SCN2Asodium channel, voltage-gated, type II, alpha subunit
Autism Reports / Total Reports
77 / 137Rare Variants / Common Variants
419 / 0Aliases
SCN2A, HBA, NAC2, HBSCI, HBSCII, Nav1.2, SCN2A1, SCN2A2, Na(v)1.2Associated Syndromes
Dravet syndromeChromosome Band
2q24.3Associated Disorders
DD/NDD, ADHD, ID, EP, EPS, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalRelevance to Autism
Recurrent mutations in the SCN2A gene have been identified in multiple individuals with ASD as described below. Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified SCN2A as a gene reaching exome-wide significance (P < 2.5E-06). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Molecular Function
voltage-gated ion channel essential for the generation and propagation of action potentials, chiefly in nerve and muscle.
External Links
SFARI Genomic Platforms
Reports related to SCN2A (137 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier | Kaplan MR , et al. (2001) | No | - |
| 2 | Highly Cited | A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction | Sugawara T , et al. (2001) | No | Febrile seizures |
| 3 | Primary | Sodium channels SCN1A, SCN2A and SCN3A in familial autism | Weiss LA , et al. (2003) | Yes | - |
| 4 | Highly Cited | A targeting motif involved in sodium channel clustering at the axonal initial segment | Garrido JJ , et al. (2003) | No | - |
| 5 | Support | A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline | Kamiya K , et al. (2004) | No | Autistic behavior |
| 6 | Recent Recommendation | The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation | Tahiliani M , et al. (2007) | No | - |
| 7 | Recent Recommendation | Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences | Martin MS , et al. (2007) | No | - |
| 8 | Support | Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy | Klassen T , et al. (2011) | No | - |
| 9 | Support | De novo mutations revealed by whole-exome sequencing are strongly associated with autism | Sanders SJ , et al. (2012) | Yes | - |
| 10 | Support | De novo gene disruptions in children on the autistic spectrum | Iossifov I , et al. (2012) | Yes | - |
| 11 | Support | Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study | Rauch A , et al. (2012) | No | Epilepsy, ASD |
| 12 | Support | Diagnostic exome sequencing in persons with severe intellectual disability | de Ligt J , et al. (2012) | No | Epilepsy, ASD |
| 13 | Recent Recommendation | Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings | Touma M , et al. (2013) | No | - |
| 14 | Support | Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 | Carvill GL , et al. (2013) | No | ID, ASD, DD |
| 15 | Support | Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing | Jiang YH , et al. (2013) | Yes | - |
| 16 | Positive Association | De novo mutations in epileptic encephalopathies | Epi4K Consortium , et al. (2013) | No | IS, LGS, DD, ID, ASD, ADHD |
| 17 | Support | - | Celle ME , et al. (2013) | No | Autistic features |
| 18 | Support | Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities | Baasch AL , et al. (2014) | No | ID |
| 19 | Support | De novo SCN2A splice site mutation in a boy with Autism spectrum disorder | Tavassoli T , et al. (2014) | Yes | - |
| 20 | Support | De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies | EuroEPINOMICS-RES Consortium , et al. (2014) | Yes | - |
| 21 | Recent Recommendation | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 22 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 23 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | Yes | DD, ID, epilepsy/seizures |
| 24 | Support | Whole-genome sequencing of quartet families with autism spectrum disorder | Yuen RK , et al. (2015) | Yes | - |
| 25 | Support | Excess of rare, inherited truncating mutations in autism | Krumm N , et al. (2015) | Yes | - |
| 26 | Support | Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders | Codina-Sol M , et al. (2015) | Yes | - |
| 27 | Recent Recommendation | Incorporating Functional Information in Tests of Excess De Novo Mutational Load | Jiang Y , et al. (2015) | No | - |
| 28 | Support | Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder | Tammimies K , et al. (2015) | Yes | - |
| 29 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 30 | Support | Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms | D'Gama AM , et al. (2015) | Yes | - |
| 31 | Support | Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target? | Horvath GA , et al. (2015) | Yes | Ataxia, hypotonia, cerebral/cerebellar atrophy |
| 32 | Recent Recommendation | Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease | Johnson MR , et al. (2015) | No | - |
| 33 | Recent Recommendation | Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA | Turner TN et al. (2016) | Yes | - |
| 34 | Recent Recommendation | Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a | Calhoun JD , et al. (2016) | No | - |
| 35 | Support | Episodic ataxia associated with a de novo SCN2A mutation | Leach EL , et al. (2016) | Yes | Ataxia, hypotonia, cerebellar atrophy |
| 36 | Support | Mutations in HECW2 are associated with intellectual disability and epilepsy | Halvardson J , et al. (2016) | Yes | - |
| 37 | Support | Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability | Lelieveld SH et al. (2016) | No | - |
| 38 | Support | Genome-wide characteristics of de novo mutations in autism | Yuen RK et al. (2016) | Yes | - |
| 39 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
| 40 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families | Trujillano D , et al. (2016) | No | Hypotonia |
| 41 | Support | Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes | Parrini E , et al. (2016) | No | - |
| 42 | Support | Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases | Stessman HA , et al. (2017) | Yes | - |
| 43 | Recent Recommendation | Opposing Effects on Na V 1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures | Ben-Shalom R , et al. (2017) | No | - |
| 44 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
| 45 | Recent Recommendation | Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders | Wolff M , et al. (2017) | No | ASD, ID |
| 46 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | No | - |
| 47 | Support | Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains | Geisheker MR , et al. (2017) | Yes | - |
| 48 | Support | Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients | Chrot E , et al. (2017) | No | - |
| 49 | Recent Recommendation | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder | Lim ET , et al. (2017) | Yes | - |
| 50 | Support | Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders | Li J , et al. (2017) | Yes | - |
| 51 | Support | Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder | Krupp DR , et al. (2017) | Yes | - |
| 52 | Support | High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies | Hamdan FF , et al. (2017) | No | DD/ID |
| 53 | Support | Dynamic action potential clamp predicts functional separation in mild familial and severe de novo forms of SCN2A epilepsy | Berecki G , et al. (2018) | No | - |
| 54 | Support | - | Pin Fee Chong et al. (2018) | Yes | - |
| 55 | Support | Nonsyndromic intellectual disability with novel heterozygous SCN2A mutation and epilepsy | Yokoi T , et al. (2018) | No | - |
| 56 | Support | - | Kathrin Nickel et al. (2018) | Yes | - |
| 57 | Support | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
| 58 | Support | Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype | Ouss L , et al. (2019) | No | ASD |
| 59 | Support | Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes | Xiong J , et al. (2019) | Yes | Epilepsy/seizures |
| 60 | Support | Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort | Callaghan DB , et al. (2019) | Yes | DD, ID |
| 61 | Support | The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children | Long S , et al. (2019) | Yes | - |
| 62 | Support | Characterization of intellectual disability and autism comorbidity through gene panel sequencing | Aspromonte MC , et al. (2019) | Yes | - |
| 63 | Recent Recommendation | The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex | Spratt PWE , et al. (2019) | No | - |
| 64 | Support | Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability | Borlot F , et al. (2019) | No | Autistic features |
| 65 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
| 66 | Support | Autism risk in offspring can be assessed through quantification of male sperm mosaicism | Breuss MW , et al. (2019) | Yes | - |
| 67 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 68 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
| 69 | Support | Genetic landscape of autism spectrum disorder in Vietnamese children | Tran KT et al. (2020) | Yes | - |
| 70 | Support | Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability | Chevarin M et al. (2020) | No | Marfanoid habitus |
| 71 | Support | Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy | Lee J et al. (2020) | Yes | - |
| 72 | Support | Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurodevelopmental disorders | van der Werf IM et al. (2020) | No | ASD, ID, psychomotor retardation |
| 73 | Support | Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression | Yin J et al. (2020) | Yes | Developmental regression |
| 74 | Support | Functional and pharmacological evaluation of a novel SCN2A variant linked to early-onset epilepsy | Adney SK et al. (2020) | No | Autistic features |
| 75 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | DD, ID |
| 76 | Support | - | Alonso-Gonzalez A et al. (2021) | Yes | - |
| 77 | Support | - | Rodin RE et al. (2021) | Yes | - |
| 78 | Support | - | Liu L et al. (2021) | No | DD |
| 79 | Support | - | Wang HG et al. (2021) | Yes | - |
| 80 | Support | - | Zhang J et al. (2021) | No | - |
| 81 | Support | - | Spratt PWE et al. (2021) | No | - |
| 82 | Recent Recommendation | - | Rosenthal SB et al. (2021) | Yes | - |
| 83 | Support | - | Pode-Shakked B et al. (2021) | No | - |
| 84 | Support | - | Mahjani B et al. (2021) | Yes | - |
| 85 | Support | - | Chen S et al. (2021) | Yes | Epilepsy/seizures |
| 86 | Support | - | Xiang J et al. (2021) | No | - |
| 87 | Support | - | Richardson R et al. (2022) | No | ASD or autistic features, stereotypy |
| 88 | Support | - | Sheth H et al. (Nov-) | Yes | - |
| 89 | Support | - | Epifanio R et al. (2021) | No | ASD, DD |
| 90 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
| 91 | Support | - | Ma Z et al. (2022) | Yes | - |
| 92 | Support | - | Mangano GD et al. (2022) | Yes | - |
| 93 | Support | - | Hieu NLT et al. (2022) | No | - |
| 94 | Support | - | Echevarria-Cooper DM et al. (2022) | No | DD, autistic features |
| 95 | Support | - | Chuan Z et al. (2022) | No | DD, ID, stereotypy |
| 96 | Recent Recommendation | - | Berecki G et al. (2022) | No | ASD/ID |
| 97 | Support | - | Sharkov A et al. (2022) | No | Autistic features, stereotypy |
| 98 | Support | - | Hu C et al. (2022) | Yes | - |
| 99 | Support | - | Levchenko O et al. (2022) | No | - |
| 100 | Support | - | Zhou X et al. (2022) | Yes | ADHD, SCZ, epilepsy/seizures |
| 101 | Support | - | Yuan B et al. (2023) | Yes | - |
| 102 | Recent Recommendation | - | Weinschutz Mendes H et al. (2023) | Yes | - |
| 103 | Support | - | Miyake N et al. (2023) | Yes | - |
| 104 | Support | - | Spataro N et al. (2023) | No | Autistic features |
| 105 | Support | - | Hu C et al. (2023) | Yes | - |
| 106 | Recent Recommendation | - | Asadollahi R et al. (2023) | Yes | Epilepsy/seizures |
| 107 | Support | - | Zhang Y et al. (2023) | Yes | DD, ID, epilepsy/seizures |
| 108 | Support | - | Wang J et al. (2023) | Yes | - |
| 109 | Support | - | Bartolomaeus T et al. (2023) | No | - |
| 110 | Support | - | Kipkemoi P et al. (2023) | Yes | - |
| 111 | Support | - | Balasar et al. (2023) | No | Epilepsy/seizures |
| 112 | Support | - | Sanchis-Juan A et al. (2023) | No | DD |
| 113 | Support | - | Sheth F et al. (2023) | Yes | DD, ID, epilepsy/seizures |
| 114 | Support | - | Ko YJ et al. (2023) | No | - |
| 115 | Support | - | Mona Abdi et al. (2023) | Yes | DD, ID |
| 116 | Support | - | Melody Li et al. (2023) | Yes | - |
| 117 | Support | - | Ana Karen Sandoval-Talamantes et al. (2023) | Yes | - |
| 118 | Support | - | Erica Rosina et al. (2024) | No | - |
| 119 | Recent Recommendation | - | Kuokuo Li et al. (2024) | Yes | - |
| 120 | Support | - | Miaomiao Mao et al. (2024) | No | ASD |
| 121 | Support | - | Emily A Innes et al. (2024) | No | ASD, ADHD, DD |
| 122 | Support | - | Luigi Vetri et al. (2024) | No | ASD |
| 123 | Support | - | Omri Bar et al. (2024) | Yes | OCD, ID, epilepsy/seizures |
| 124 | Recent Recommendation | - | Andrew D Nelson et al. (2024) | Yes | - |
| 125 | Support | - | Chad O Brown et al. (2024) | Yes | - |
| 126 | Support | - | Magdalena Badura-Stronka et al. (2024) | No | - |
| 127 | Support | - | Purvi Majethia et al. (2024) | No | ASD, DD |
| 128 | Recent Recommendation | - | Chenyu Wang et al. (2024) | Yes | - |
| 129 | Support | - | Tamam Khalaf et al. (2024) | Yes | - |
| 130 | Recent Recommendation | - | Jiaxiang Wu et al. () | Yes | - |
| 131 | Support | - | Marta Viggiano et al. (2024) | Yes | ID |
| 132 | Support | - | Linghan Jia et al. () | No | - |
| 133 | Support | - | Ahmed Eltokhi et al. (2024) | Yes | - |
| 134 | Support | - | Anne T Berg et al. () | No | ASD, ID |
| 135 | Support | - | Ruohao Wu et al. (2024) | Yes | - |
| 136 | Support | - | Axel Schmidt et al. (2024) | No | ID |
| 137 | Support | - | Suhua Chang et al. () | Yes | - |
Rare Variants (419)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | Unknown | - | - | 32477112 | Lee J et al. (2020) | |
| - | - | copy_number_loss | Unknown | - | - | 31273778 | Borlot F , et al. (2019) | |
| - | - | copy_number_loss | De novo | - | - | 29929112 | Pin Fee Chong et al. (2018) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 24080482 | Celle ME , et al. (2013) | |
| - | - | copy_number_loss | De novo | - | Multiplex | 25621899 | Yuen RK , et al. (2015) | |
| c.2566C>T | p.Arg856Ter | stop_gained | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| c.605+1G>A | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.605+1G>T | - | splice_site_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.267+5G>C | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.605+1G>A | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | p.Ile891Thr | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.304C>T | p.Arg102Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.796G>T | p.Gly266Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.823C>T | p.Arg275Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.667C>T | p.Arg223Ter | stop_gained | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.823C>T | p.Arg275Ter | stop_gained | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1177-1G>A | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2562+2T>C | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4254+1G>T | - | splice_site_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.2017-2A>C | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2150-2A>C | - | splice_site_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2150-2A>G | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3521-1G>T | - | splice_site_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4447-2A>G | - | splice_site_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2563-1G>A | - | splice_site_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| c.605+1G>A | - | splice_site_variant | De novo | - | - | 37035742 | Zhang Y et al. (2023) | |
| c.1927A>T | p.Lys643Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2548C>T | p.Arg850Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.2566C>T | p.Arg856Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.2566C>T | p.Arg856Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2877C>A | p.Cys959Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1570C>T | p.Arg524Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.386+4T>C | - | splice_region_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3850-2A>C | - | splice_site_variant | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.386+2T>C | - | splice_site_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.605+1G>T | - | splice_site_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.698-1G>T | - | splice_site_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.56G>A | p.Arg19Lys | missense_variant | - | - | - | 11371648 | Sugawara T , et al. (2001) | |
| c.3703C>T | p.Arg1235Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4303C>T | p.Arg1435Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.5125C>T | p.Gln1709Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.5626C>T | p.Arg1876Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5644C>T | p.Arg1882Ter | stop_gained | De novo | - | - | 34800434 | Chen S et al. (2021) | |
| c.3892G>T | p.Glu1298Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4303C>T | p.Arg1435Ter | stop_gained | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4591C>T | p.Gln1531Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4876C>T | p.Arg1626Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3849+4A>T | - | splice_region_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1819C>T | p.Arg607Ter | stop_gained | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.2566C>T | p.Arg856Ter | stop_gained | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.1570C>T | p.Arg524Ter | stop_gained | De novo | - | - | 37035742 | Zhang Y et al. (2023) | |
| c.843G>A | p.Trp281Ter | stop_gained | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.304C>T | p.Arg102Ter | stop_gained | De novo | - | - | 15028761 | Kamiya K , et al. (2004) | |
| - | - | copy_number_loss | De novo | - | Multiplex | 30071822 | Kathrin Nickel et al. (2018) | |
| c.868A>G | p.Ile290Val | missense_variant | De novo | - | - | 28831199 | Li J , et al. (2017) | |
| c.254A>G | p.Tyr85Cys | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.3703C>T | p.Arg1235Ter | stop_gained | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4303C>T | p.Arg1435Ter | stop_gained | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5147G>A | p.Trp1716Ter | stop_gained | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.3676-4del | - | splice_site_variant | De novo | - | - | 35053762 | Epifanio R et al. (2021) | |
| c.1571G>A | p.Arg524Gln | missense_variant | - | - | - | 11371648 | Sugawara T , et al. (2001) | |
| c.1429G>T | p.Ala477Ser | missense_variant | De novo | - | - | 28831199 | Li J , et al. (2017) | |
| c.562C>T | p.Arg188Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.796G>A | p.Gly266Arg | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 26749308 | Turner TN et al. (2016) | |
| c.5318C>T | p.Ala1773Val | missense_variant | De novo | - | - | 28831199 | Li J , et al. (2017) | |
| c.4309-2A>G | - | splice_site_variant | De novo | - | Simplex | 37645600 | Ko YJ et al. (2023) | |
| c.1094C>T | p.Thr365Met | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1136G>A | p.Arg379His | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1138C>T | p.Leu380Phe | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1165C>T | p.Leu389Phe | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1691G>T | p.Gly564Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1840C>T | p.Pro614Ser | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1841C>T | p.Pro614Leu | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2050C>T | p.Arg684Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2351C>T | p.Thr784Met | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2435C>T | p.Ala812Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2695G>A | p.Gly899Ser | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2809C>T | p.Arg937Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2860G>A | p.Ala954Thr | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1184G>A | p.Arg395His | missense_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| c.3G>A | p.Met1? | initiator_codon_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.605+1G>A | - | splice_site_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.4193G>A | p.Trp1398Ter | stop_gained | De novo | - | - | 23033978 | de Ligt J , et al. (2012) | |
| c.2227A>T | p.Lys743Ter | stop_gained | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
| c.3767A>T | p.Glu1256Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3883G>T | p.Gly1295Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5138C>T | p.Ser1713Phe | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.5272A>C | p.Ser1758Arg | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.5318C>T | p.Ala1773Val | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.5381A>T | p.Asp1794Val | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.5704C>T | p.Arg1902Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5921C>T | p.Ser1974Leu | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4501A>G | p.Met1501Val | missense_variant | De novo | - | - | 34800434 | Chen S et al. (2021) | |
| c.3399G>C | p.Glu1133Asp | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3986C>T | p.Ala1329Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.5129T>A | p.Ile1710Asn | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.5465C>G | p.Ala1822Gly | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2197G>C | p.Ala733Pro | missense_variant | Unknown | - | - | 27824329 | Wang T , et al. (2016) | |
| c.2558G>A | p.Arg853Gln | missense_variant | De novo | - | - | 31139143 | Long S , et al. (2019) | |
| c.1837G>A | p.Val613Met | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.620T>C | p.Phe207Ser | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.680C>T | p.Thr227Ile | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.710T>A | p.Ile237Asn | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.781G>A | p.Val261Met | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.788C>T | p.Ala263Val | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.1251A>C | p.Ile417%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2566C>T | p.Arg856Ter | stop_gained | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.2701C>T | p.Gln901Ter | stop_gained | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.1534G>T | p.Glu512Ter | stop_gained | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.3956G>C | p.Arg1319Pro | missense_variant | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.3961G>A | p.Glu1321Lys | missense_variant | De novo | - | - | 31139143 | Long S , et al. (2019) | |
| c.4963A>G | p.Met1655Val | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.1028A>G | p.Asp343Gly | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.1267G>C | p.Val423Leu | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.1270G>T | p.Val424Leu | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.1289A>C | p.Glu430Ala | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.1835T>C | p.Phe612Ser | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2197G>A | p.Ala733Thr | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2483G>T | p.Gly828Val | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2558G>A | p.Arg853Gln | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2558G>A | p.Arg853Gln | missense_variant | Unknown | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2567G>A | p.Arg856Gln | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2588C>T | p.Ser863Phe | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2642T>C | p.Leu881Pro | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2645G>A | p.Gly882Glu | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2660T>C | p.Val887Ala | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2684T>C | p.Phe895Ser | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2695G>A | p.Gly899Ser | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2722A>G | p.Lys908Glu | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2790C>A | p.His930Gln | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2995G>A | p.Glu999Lys | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.2558G>A | p.Arg853Gln | missense_variant | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
| c.2021C>A | p.Thr674Lys | missense_variant | De novo | - | - | 33432195 | Rodin RE et al. (2021) | |
| - | p.Asn503LysfsTer19 | frameshift_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4543C>T | p.Arg1515Ter | stop_gained | De novo | - | - | 34894057 | Richardson R et al. (2022) | |
| c.3703C>T | p.Arg1235Ter | stop_gained | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.4641C>G | p.Thr1547%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4303C>T | p.Arg1435Ter | stop_gained | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.4491C>A | p.Tyr1497Ter | stop_gained | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.1552G>T | p.Glu518Ter | stop_gained | De novo | - | Simplex | 37543562 | Sheth F et al. (2023) | |
| c.1570C>T | p.Arg524Ter | stop_gained | De novo | - | Simplex | 39126614 | Suhua Chang et al. () | |
| c.3631G>A | p.Glu1211Lys | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.3667G>C | p.Gly1223Arg | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.3841A>T | p.Ile1281Phe | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.3955C>T | p.Arg1319Trp | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.3956G>A | p.Arg1319Gln | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.3956G>A | p.Arg1319Gln | missense_variant | Unknown | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4025T>C | p.Leu1342Pro | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4498G>A | p.Ala1500Thr | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4591C>A | p.Gln1531Lys | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4608C>A | p.Ser1536Arg | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4633A>G | p.Met1545Val | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4642A>G | p.Met1548Val | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4791T>A | p.Phe1597Leu | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4864C>T | p.Pro1622Ser | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4879G>A | p.Val1627Met | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4886G>A | p.Arg1629His | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4919T>G | p.Ile1640Ser | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4952T>G | p.Phe1651Cys | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4954G>C | p.Ala1652Pro | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4967C>T | p.Ser1656Phe | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4993C>T | p.Leu1665Phe | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5231G>A | p.Gly1744Glu | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5318C>T | p.Ala1773Val | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5431C>G | p.Gln1811Glu | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5645G>C | p.Arg1882Pro | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5645G>T | p.Arg1882Leu | missense_variant | Unknown | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5798A>T | p.Lys1933Met | missense_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4501A>G | p.Met1501Val | missense_variant | De novo | - | - | 31031587 | Xiong J , et al. (2019) | |
| - | p.Cys1170ValfsTer15 | frameshift_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.571T>G | p.Trp191Gly | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.751G>A | p.Val251Ile | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.788C>T | p.Ala263Val | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.83G>A | p.Arg28His | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.4822G>A | p.Gly1608Arg | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| c.2687C>T | p.Ala896Val | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.2764C>A | p.Arg922Ser | missense_variant | De novo | - | - | 31873310 | Breuss MW , et al. (2019) | |
| c.1136G>A | p.Arg379His | missense_variant | De novo | - | - | 35348308 | Mangano GD et al. (2022) | |
| c.408G>T | p.Met136Ile | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.719C>T | p.Ala240Val | missense_variant | De novo | - | - | 38256219 | Luigi Vetri et al. (2024) | |
| c.4551+1G>C | - | splice_site_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.718G>C | p.Ala240Pro | missense_variant | De novo | - | Simplex | 37645600 | Ko YJ et al. (2023) | |
| c.2016+6G>C | - | splice_region_variant | Unknown | - | Simplex | 37524782 | Balasar et al. (2023) | |
| c.1819C>T | p.Arg607Ter | stop_gained | Unknown | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.3947C>T | p.Ala1316Val | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.3967A>G | p.Met1323Val | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.4031G>A | p.Cys1344Tyr | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.4643T>C | p.Met1548Thr | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.5645G>A | p.Arg1882Gln | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.3947C>T | p.Ala1316Val | missense_variant | De novo | - | - | 35053762 | Epifanio R et al. (2021) | |
| c.4551+1G>C | - | splice_site_variant | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
| c.2715G>C | p.Lys905Asn | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.2783T>G | p.Phe928Cys | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.1289A>C | p.Glu430Ala | missense_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
| c.2387T>C | p.Leu796Pro | missense_variant | De novo | - | - | 38256219 | Luigi Vetri et al. (2024) | |
| c.756G>A | p.Met252Ile | missense_variant | Unknown | - | - | 34894057 | Richardson R et al. (2022) | |
| c.718G>C | p.Ala240Pro | missense_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.788C>T | p.Ala263Val | missense_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.578G>C | p.Trp193Ser | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.1094C>T | p.Thr365Met | missense_variant | De novo | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.2671A>G | p.Ile891Val | missense_variant | De novo | - | Simplex | 37645600 | Ko YJ et al. (2023) | |
| c.4492_4494del | p.Tyr1498del | inframe_deletion | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1035-7A>G | - | splice_region_variant | De novo | - | Simplex | 35711923 | Sharkov A et al. (2022) | |
| c.118G>T | p.Glu40Ter | stop_gained | Familial | Paternal | - | 35053762 | Epifanio R et al. (2021) | |
| c.2877C>A | p.Cys959Ter | stop_gained | De novo | - | Simplex | 37463579 | Kipkemoi P et al. (2023) | |
| c.5645G>A | p.Arg1882Gln | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.4468A>G | p.Met1490Val | missense_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.4726G>A | p.Gly1576Arg | missense_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.2270T>C | p.Met757Thr | missense_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.2659G>C | p.Val887Leu | missense_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.476+1G>A | - | splice_site_variant | De novo | - | Simplex | 24650168 | Tavassoli T , et al. (2014) | |
| c.476+1G>A | - | splice_site_variant | De novo | - | Simplex | 28191889 | Stessman HA , et al. (2017) | |
| c.4543C>T | p.Arg1515Ter | stop_gained | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.5549A>G | p.Asp1850Gly | missense_variant | Unknown | - | Unknown | 32722525 | Yin J et al. (2020) | |
| c.4886G>A | p.Arg1629His | missense_variant | De novo | - | Simplex | 33951346 | Liu L et al. (2021) | |
| c.425del | p.Asn142ThrfsTer5 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1034G>A | p.Gly345Asp | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.1184G>C | p.Arg395Pro | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.2764C>T | p.Arg922Cys | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.2810G>A | p.Arg937His | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.2050C>T | p.Arg684Trp | missense_variant | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
| c.2545C>A | p.Leu849Ile | missense_variant | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
| c.1079C>T | p.Pro360Leu | missense_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.4543C>T | p.Arg1515Ter | stop_gained | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
| c.5641G>T | p.Glu1881Ter | stop_gained | De novo | - | Simplex | 32277047 | Chevarin M et al. (2020) | |
| c.2877C>A | p.Cys959Ter | stop_gained | De novo | - | Simplex | 22495306 | Sanders SJ , et al. (2012) | |
| c.4409G>C | p.Gly1470Ala | missense_variant | De novo | - | - | 26325558 | Tammimies K , et al. (2015) | |
| c.4823-2A>T | - | splice_site_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1060G>A | p.Val354Met | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.1067C>G | p.Ala356Gly | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.1112G>T | p.Ser371Ile | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.1136G>A | p.Arg379His | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.1165C>T | p.Leu389Phe | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.2482G>A | p.Gly828Ser | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.2764C>T | p.Arg922Cys | missense_variant | De novo | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.2809C>T | p.Arg937Cys | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.2810G>A | p.Arg937His | missense_variant | De novo | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.2860G>A | p.Ala954Thr | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.971-1G>A | - | splice_site_variant | De novo | - | Simplex | 31038196 | Callaghan DB , et al. (2019) | |
| c.3211G>A | p.Gly1071Arg | missense_variant | Familial | Paternal | - | 37007974 | Hu C et al. (2023) | |
| c.5522C>T | p.Ala1841Val | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.2193del | p.Lys731AsnfsTer7 | frameshift_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2478del | p.Phe826LeufsTer6 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4461C>G | p.Asp1487Glu | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.4904G>A | p.Arg1635Gln | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.5230G>A | p.Gly1744Arg | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.5274T>G | p.Ser1758Arg | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.5316C>G | p.Ile1772Met | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.232dup | p.Leu78ProfsTer11 | frameshift_variant | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.5230G>T | p.Gly1744Ter | stop_gained | Unknown | - | Multiplex | 28263302 | C Yuen RK et al. (2017) | |
| c.34G>A | p.Asp12Asn | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.3037G>T | p.Gly1013Ter | stop_gained | De novo | - | Simplex | 22495306 | Sanders SJ , et al. (2012) | |
| c.2765G>A | p.Arg922His | missense_variant | De novo | - | - | 38374498 | Purvi Majethia et al. (2024) | |
| c.1094C>T | p.Thr365Met | missense_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.1117G>A | p.Ala373Thr | missense_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.1841C>T | p.Pro614Leu | missense_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
| c.3347del | p.Asn1116IlefsTer2 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.5134del | p.Thr1712ProfsTer9 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1064del | p.Lys355ArgfsTer27 | frameshift_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4727del | p.Gly1576GlufsTer5 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.305G>A | p.Arg102Gln | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
| c.1117del | p.Ala373ProfsTer9 | frameshift_variant | De novo | - | - | 34858471 | Xiang J et al. (2021) | |
| c.5311T>A | p.Tyr1771Asn | missense_variant | De novo | - | Simplex | 37543562 | Sheth F et al. (2023) | |
| c.106A>G | p.Arg36Gly | missense_variant | Familial | Maternal | - | 28379373 | Wolff M , et al. (2017) | |
| c.2809C>T | p.Arg937Cys | missense_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
| c.2809C>T | p.Arg937Cys | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
| c.4474G>T | p.Glu1492Ter | stop_gained | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.4876C>T | p.Arg1626Ter | stop_gained | De novo | - | Simplex | 28191889 | Stessman HA , et al. (2017) | |
| c.3972+4A>G | - | splice_region_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.1747C>T | p.Arg583Ter | stop_gained | De novo | - | Simplex | 25969726 | Codina-Sol M , et al. (2015) | |
| c.1176+5G>A | - | splice_site_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.2562+2T>C | - | splice_site_variant | De novo | - | Simplex | 34580403 | Pode-Shakked B et al. (2021) | |
| c.3529C>T | p.Arg1177Trp | missense_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
| c.3463del | p.Glu1155AsnfsTer30 | frameshift_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.5889C>T | p.Thr1963%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.1423dup | p.Ser475LysfsTer18 | frameshift_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.605C>T | p.Ala202Val | missense_variant | Familial | Maternal | - | 28379373 | Wolff M , et al. (2017) | |
| c.4156T>C | p.Cys1386Arg | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
| c.4378G>C | p.Gly1460Arg | missense_variant | De novo | - | Simplex | 30062040 | Yokoi T , et al. (2018) | |
| c.5636T>C | p.Met1879Thr | missense_variant | De novo | - | Simplex | 32750235 | Adney SK et al. (2020) | |
| c.4782G>T | p.Trp1594Cys | missense_variant | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
| c.4976C>T | p.Ala1659Val | missense_variant | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
| c.4657G>A | p.Asp1553Asn | missense_variant | Unknown | - | Simplex | 37524782 | Balasar et al. (2023) | |
| c.781G>A | p.Val261Met | missense_variant | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.82C>T | p.Arg28Cys | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.3827G>A | p.Trp1276Ter | stop_gained | De novo | - | Simplex | 27848944 | Trujillano D , et al. (2016) | |
| c.1644T>A | p.Tyr548Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.4254+1G>A | - | splice_site_variant | De novo | - | Simplex | 32651551 | van der Werf IM et al. (2020) | |
| c.282_285del | p.Asn95LysfsTer17 | frameshift_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4581dup | p.Val1528CysfsTer7 | frameshift_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.4901G>A | p.Gly1634Asp | missense_variant | De novo | - | Simplex | 27328862 | Leach EL , et al. (2016) | |
| c.5318C>T | p.Ala1773Val | missense_variant | De novo | - | Simplex | 37805537 | Mona Abdi et al. (2023) | |
| c.2021C>A | p.Thr674Lys | missense_variant | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
| c.1959G>A | p.Val653= | synonymous_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.245A>G | p.Asp82Gly | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.100G>A | p.Ala34Thr | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.4204A>T | p.Lys1402Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.4480C>T | p.Gln1494Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1570C>T | p.Arg524Ter | stop_gained | De novo | - | Simplex | 32651551 | van der Werf IM et al. (2020) | |
| c.2558G>A | p.Arg853Gln | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.605+1G>A | - | splice_site_variant | Unknown | Not maternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.5229A>G | p.Lys1743%3D | synonymous_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.1940del | p.Ala647ValfsTer34 | frameshift_variant | De novo | - | - | 36980980 | Spataro N et al. (2023) | |
| c.3711del | p.Ile1238LeufsTer5 | frameshift_variant | De novo | - | - | 36980980 | Spataro N et al. (2023) | |
| c.5377G>A | p.Asp1793Asn | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.5645G>T | p.Arg1882Leu | missense_variant | De novo | - | Simplex | 24579881 | Baasch AL , et al. (2014) | |
| c.5230G>A | p.Gly1744Arg | missense_variant | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
| c.4468A>G | p.Met1490Val | missense_variant | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.4886G>A | p.Arg1629His | missense_variant | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.2380G>A | p.Gly794Arg | missense_variant | De novo | - | Simplex | 35887114 | Levchenko O et al. (2022) | |
| c.148C>T | p.Pro50Ser | missense_variant | Familial | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.193A>G | p.Ile65Val | missense_variant | Familial | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.640T>G | p.Ser214Ala | missense_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.2319A>G | p.Thr773%3D | synonymous_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.2622_2631del | p.Ile874MetfsTer5 | frameshift_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1456_1457del | p.Ser486PhefsTer6 | frameshift_variant | Unknown | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1563_1564del | p.Asp521GlufsTer8 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2658delinsTT | p.Leu886PhefsTer20 | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.5704C>T | p.Arg1902Cys | missense_variant | De novo | - | Multiplex | 12610651 | Weiss LA , et al. (2003) | |
| c.4259C>T | p.Thr1420Met | missense_variant | De novo | - | Simplex | 22542183 | Iossifov I , et al. (2012) | |
| c.1136G>A | p.Arg379His | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2810G>A | p.Arg937His | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1184G>A | p.Arg395His | missense_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.2467T>G | p.Trp823Gly | missense_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.2774T>C | p.Met925Thr | missense_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.788C>T | p.Ala263Val | missense_variant | De novo | - | Simplex | 27334371 | Halvardson J , et al. (2016) | |
| c.305G>A | p.Arg102Gln | missense_variant | De novo | - | Simplex | 31038196 | Callaghan DB , et al. (2019) | |
| c.248C>T | p.Pro83Leu | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.4180C>T | p.Gln1394Ter | stop_gained | De novo | - | Multiplex | 38519481 | Marta Viggiano et al. (2024) | |
| c.3277_3278del | p.Met1093ValfsTer7 | frameshift_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.4018_4039del | p.Val1340PhefsTer3 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2050C>T | p.Arg684Trp | missense_variant | Familial | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.4822G>A | p.Gly1608Arg | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.5704C>T | p.Arg1902Cys | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.4644G>C | p.Met1548Ile | missense_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.4886G>A | p.Arg1629His | missense_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.5192G>A | p.Cys1731Tyr | missense_variant | De novo | - | Simplex | 34894057 | Richardson R et al. (2022) | |
| c.644C>A | p.Ala215Asp | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| - | - | copy_number_gain | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.5500_5503dup | p.Asn1835ThrfsTer17 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1821_1822del | p.Asp609LeufsTer37 | frameshift_variant | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.4550_4551del | p.Ala1517GlufsTer9 | frameshift_variant | De novo | - | - | 37035742 | Zhang Y et al. (2023) | |
| c.232del | p.Leu78TrpfsTer15 | frameshift_variant | De novo | - | Simplex | 32193494 | Tran KT et al. (2020) | |
| c.3061del | p.Ile1021TyrfsTer16 | frameshift_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.2380G>A | p.Gly794Arg | splice_site_variant | De novo | - | Simplex | 26647175 | Horvath GA , et al. (2015) | |
| c.3929del | p.Ala1310ValfsTer2 | frameshift_variant | De novo | - | - | 28191889 | Stessman HA , et al. (2017) | |
| c.2809C>T | p.Arg937Cys | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1270G>T | p.Val424Leu | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.788C>T | p.Ala263Val | missense_variant | De novo | - | Simplex | 32651551 | van der Werf IM et al. (2020) | |
| c.5198del | p.Pro1733LeufsTer36 | frameshift_variant | De novo | - | Simplex | 33951346 | Liu L et al. (2021) | |
| c.1082del | p.Asn361ThrfsTer21 | frameshift_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.4796_4797del | p.Phe1599CysfsTer14 | frameshift_variant | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.5711_5712del | p.Gln1904ArgfsTer22 | frameshift_variant | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.1154del | p.Phe385SerfsTer8 | frameshift_variant | De novo | - | Simplex | 34979677 | Sheth H et al. (Nov-) | |
| c.4160_4161del | p.Lys1387SerfsTer4 | frameshift_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.5131_5137del | p.Thr1711LeufsTer8 | frameshift_variant | De novo | - | - | 28379373 | Wolff M , et al. (2017) | |
| c.82C>T | p.Arg28Cys | missense_variant | Familial | Maternal | Simplex | 23849776 | Jiang YH , et al. (2013) | |
| c.5318C>T | p.Ala1773Val | missense_variant | Unknown | - | Multiplex | 34894057 | Richardson R et al. (2022) | |
| c.1094C>T | p.Thr365Met | missense_variant | Familial | Maternal | - | 28628100 | Geisheker MR , et al. (2017) | |
| c.664C>T | p.Leu222Phe | missense_variant | Familial | Maternal | - | 31209962 | Aspromonte MC , et al. (2019) | |
| c.3820T>G | p.Trp1274Gly | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.3914T>G | p.Leu1305Arg | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.4509del | p.Lys1503AsnfsTer26 | frameshift_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.3670G>T | p.Ala1224Ser | missense_variant | Familial | Paternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.4876del | p.Arg1626GlufsTer2 | frameshift_variant | De novo | - | Simplex | 27525107 | Yuen RK et al. (2016) | |
| c.3598A>G | p.Thr1200Ala | missense_variant | Familial | - | Multiplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1691G>T | p.Gly564Val | missense_variant | De novo | - | Multiplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.3631G>A | p.Glu1211Lys | missense_variant | De novo | - | Simplex | 32651551 | van der Werf IM et al. (2020) | |
| c.5726C>T | p.Ala1909Val | missense_variant | Familial | Maternal | Simplex | 37543562 | Sheth F et al. (2023) | |
| c.1508dup | p.Asn503LysfsTer19 | frameshift_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
| c.1785del | p.Asp595GlufsTer46 | frameshift_variant | De novo | - | Simplex | 36973392 | Miyake N et al. (2023) | |
| c.4179_4182del | p.Asn1393LysfsTer8 | frameshift_variant | De novo | - | - | 35053762 | Epifanio R et al. (2021) | |
| c.4606A>G | p.Ser1536Gly | missense_variant | Unknown | - | Multiplex | 37460657 | Bartolomaeus T et al. (2023) | |
| c.4578T>G | p.Asp1526Glu | missense_variant | Familial | Paternal | Simplex | 38256266 | Omri Bar et al. (2024) | |
| c.4876del | p.Arg1626GlufsTer2 | frameshift_variant | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.1800del | p.Phe601LeufsTer40 | frameshift_variant | De novo | - | Simplex | 32094338 | Husson T , et al. (2020) | |
| c.4904G>A | p.Arg1635Gln | missense_variant | De novo | - | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
| c.1304_1305del | p.Thr435IlefsTer5 | frameshift_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.3370A>T | p.Ser1124Cys | missense_variant | Familial | Maternal | Simplex | 28867142 | Krupp DR , et al. (2017) | |
| c.4533del | p.Lys1511AsnfsTer18 | frameshift_variant | De novo | - | Simplex | 38764027 | Ruohao Wu et al. (2024) | |
| c.562C>T | p.Arg188Trp | missense_variant | Familial | Paternal | Simplex | 11371648 | Sugawara T , et al. (2001) | |
| c.1318_1349del | p.Glu440ArgfsTer20 | frameshift_variant | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
| c.1533_1536del | p.Lys511AsnfsTer21 | frameshift_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.1648_1649del | p.Lys550GlufsTer24 | frameshift_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.4796_4797del | p.Phe1599CysfsTer14 | frameshift_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.3331_3332del | p.Glu1111IlefsTer2 | frameshift_variant | De novo | - | Simplex | 35571021 | Chuan Z et al. (2022) | |
| c.191_192del | p.Phe64TyrfsTer24 | frameshift_variant | Unknown | Not maternal | - | 33004838 | Wang T et al. (2020) | |
| c.1831_1832del | p.Leu611ValfsTer35 | frameshift_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
| c.5333del | p.Asn1778ThrfsTer13 | frameshift_variant | De novo | - | Simplex | 27479843 | Lelieveld SH et al. (2016) | |
| c.2545C>A | p.Leu849Ile | missense_variant | Familial | Paternal | Simplex | 28628100 | Geisheker MR , et al. (2017) | |
| c.2789A>C | p.His930Pro | missense_variant | Unknown | - | - | 38003033 | Ana Karen Sandoval-Talamantes et al. (2023) | |
| c.1318_1349del | p.Glu440ArgfsTer20 | frameshift_variant | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.2674G>A | p.Val892Ile | missense_variant | Familial | Paternal | Multiplex | 34894057 | Richardson R et al. (2022) | |
| c.668G>A | p.Arg223Gln | missense_variant | Unknown | - | Extended multiplex | 38160512 | Emily A Innes et al. (2024) | |
| c.668G>A | p.Arg223Gln | missense_variant | Unknown | - | Multi-generational | 38160512 | Emily A Innes et al. (2024) | |
| c.5890G>A | p.Asp1964Asn | missense_variant | Unknown | - | - | 38003033 | Ana Karen Sandoval-Talamantes et al. (2023) | |
| c.1318_1349del | p.Glu440ArgfsTer20 | frameshift_variant | De novo | - | Multiplex | 23849776 | Jiang YH , et al. (2013) | |
| c.1499_1500del | p.Glu500AlafsTer21 | frameshift_variant | De novo | - | Simplex | 35887114 | Levchenko O et al. (2022) | |
| c.1561_1562del | p.Asp521GlnfsTer8 | frameshift_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.60_61delinsC | p.Glu20AspfsTer73 | frameshift_variant | De novo | - | Simplex | 38041506 | Erica Rosina et al. (2024) | |
| c.3929del | p.Ala1310ValfsTer2 | frameshift_variant | De novo | - | Multiplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.4972C>T | p.Pro1658Ser | missense_variant | Unknown | - | Simplex | 38328757 | Magdalena Badura-Stronka et al. (2024) | |
| c.2614_2615dup | p.Ile873ArgfsTer10 | frameshift_variant | De novo | - | Simplex | 38041506 | Erica Rosina et al. (2024) | |
| c.605+1G>A | - | splice_site_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.4581del | p.Phe1527LeufsTer2 | frameshift_variant | Unknown | Not maternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.2057_2058insA | p.Ser686ArgfsTer34 | frameshift_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.304C>T | p.Arg102Ter | stop_gained | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.4509_4510delinsT | p.Lys1503AsnfsTer26 | frameshift_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
| c.1318_1349del | p.Glu440ArgfsTer20 | frameshift_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.4264A>G | p.Lys1422Glu | missense_variant | De novo | - | Simplex | 25262651 | EuroEPINOMICS-RES Consortium , et al. (2014) | |
| c.668G>A | p.Arg223Gln | missense_variant | Familial | Paternal | Multi-generational | 38160512 | Emily A Innes et al. (2024) | |
| c.2674G>A | p.Val892Ile | missense_variant | Familial | Paternal | Multi-generational | 38160512 | Emily A Innes et al. (2024) | |
| c.2932T>C | p.Phe978Leu | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.4780T>A | p.Trp1594Arg | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.5638G>A | p.Glu1880Lys | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.1437del | p.Ile480Ter | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.515T>G | p.Ile172Ser | missense_variant | Familial | Maternal | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.1696del | p.Leu566PhefsTer75 | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Score Delta: Score remained at 1
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
4/1/2021
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
1/1/2021
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
10/1/2020
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
7/1/2020
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Reports Added
[Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurodevelopmental disorders2020] [Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression2020] [Functional and pharmacological evaluation of a novel SCN2A variant linked to early-onset epilepsy2020]4/1/2020
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Reports Added
[Genetic landscape of autism spectrum disorder in Vietnamese children2020] [Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability2020] [Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy2020]1/1/2020
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Reports Added
[Autism risk in offspring can be assessed through quantification of male sperm mosaicism.2019] [Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020] [Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use.2020]10/1/2019
Score remained at 1
New Scoring Scheme
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
7/1/2019
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Reports Added
[The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children.2019] [Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019] [The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex.2019] [Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability.2019]4/1/2019
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Reports Added
[Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype.2019] [Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.2019] [Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.2019]1/1/2019
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
7/1/2018
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
10/1/2017
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR ? 0.01, meaning that this gene had a ? 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Reports Added
[Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.2017] [Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.2017] [High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.2017]7/1/2017
Score remained at 1
Description
Rare ASD-associated variants in the SCN2A gene were initially identified in a study by Weiss and colleagues in 2003 based on exon screening in a region of linkage with autism (PMID 12610651). Sanders et al., 2012 subsequently reported 2 de novo loss-of-function (LoF) variants in SCN2A among 200 ASD families from the Simons Simplex Collection (PMID 22495306). A third de novo LoF variant in the SCN2A gene was identified in a simplex ASD case in Tavassoli et al., 2014; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was identified in a female ASD proband with intellectual disability in Jiang et al., 2013; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified SCN2A as a gene meeting high statistical significance with a FDR ? 0.01, meaning that this gene had a ? 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect (PMID 28256214). Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients (PMID 28379373).
Reports Added
[Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.2017] [Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017] [Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017]4/1/2017
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect. Wolff et al., 2017 reported the phenotypes of 71 previously unpublished patients with SCN2A mutations; ASD was reported as a phenotype in 23 of these patients.
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [De novo SCN2A splice site mutation in a boy with Autism spectrum disorder.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscula...2014] [A missense mutation of the Na channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.2001] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier.2001] [A targeting motif involved in sodium channel clustering at the axonal initial segment.2003] [The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation.2007] [Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncod...2007] [Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings.2013] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015] [Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA2016] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a.2016] [Mutations in HECW2 are associated with intellectual disability and epilepsy.2016] [Episodic ataxia associated with a de novo SCN2A mutation.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Genome-wide characteristics of de novo mutations in autism2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile ...2017] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]1/1/2017
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Functional analysis of ASD-associated de novo missense and likely gene disruptive SCN2A variants identified in probands from the Simons Simplex Collection and the Autism Sequencing Consortium using whole-cell voltage-clamp electrophysiology in Ben-Shalom et al., 2017 found that these variants dampened or eliminated channel function, consistent with a loss-of-function effect.
Reports Added
[Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile ...2017] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017]10/1/2016
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).
7/1/2016
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).
Reports Added
[Mutations in HECW2 are associated with intellectual disability and epilepsy.2016] [Episodic ataxia associated with a de novo SCN2A mutation.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Genome-wide characteristics of de novo mutations in autism2016]4/1/2016
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [De novo SCN2A splice site mutation in a boy with Autism spectrum disorder.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscula...2014] [A missense mutation of the Na channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.2001] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier.2001] [A targeting motif involved in sodium channel clustering at the axonal initial segment.2003] [The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation.2007] [Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncod...2007] [Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings.2013] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015] [Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA2016] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a.2016]1/1/2016
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [De novo SCN2A splice site mutation in a boy with Autism spectrum disorder.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscula...2014] [A missense mutation of the Na channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.2001] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier.2001] [A targeting motif involved in sodium channel clustering at the axonal initial segment.2003] [The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation.2007] [Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncod...2007] [Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings.2013] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.2015] [Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA2016] [The contribution of de novo coding mutations to autism spectrum disorder2014]7/1/2015
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [De novo SCN2A splice site mutation in a boy with Autism spectrum disorder.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscula...2014] [A missense mutation of the Na channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.2001] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier.2001] [A targeting motif involved in sodium channel clustering at the axonal initial segment.2003] [The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation.2007] [Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncod...2007] [Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings.2013] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015]4/1/2015
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LoF in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).
1/1/2015
Score remained at 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LGD in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).
10/1/2014
Decreased from 2 to 1
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LGD in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified SCN2A as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).
7/1/2014
Increased from No data to 2
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LGD in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776).
4/1/2014
Increased from No data to 2
Description
Rare variants in the SCN2A gene were identified in a single study based on exon screening in a region of linkage with autism (PMID: 12610651). PMID 22495306 reported 2 de novo LGD in SCN2A among 200 ASD families. A third de novo LoF variant in the SCN2A gene was recently identified in a simplex ASD case; this variant was not observed in dbSNP or other genomic databases (PMID 24650168). A fourth de novo LoF variant in SCN2A was recently identified in a female ASD proband with intellectual disability; this variant was not present in a female sibling with ASD but normal IQ (PMID 23849776).
Krishnan Probability Score
Score 0.6089135525395
Ranking 272/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99999999231438
Ranking 132/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.998
Ranking 10/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 3.5684477595055E-10
Ranking 2/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 120
Ranking 6/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.53627129374455
Ranking 302/20870 scored genes
[Show Scoring Methodology]
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| ARHGEF10L | Rho guanine nucleotide exchange factor (GEF) 10-like | Human | Protein Binding | 55160 | Q9HCE6 |
| FGF14 | fibroblast growth factor 14 | Human | Direct Regulation | 2259 | Q92915 |
| Scn4b | sodium channel, voltage-gated, type IV, beta | Rat | Protein Binding | 315611 | Q7M730 |