SCN1Asodium channel, voltage-gated, type I, alpha subunit
Autism Reports / Total Reports
33 / 99Rare Variants / Common Variants
264 / 2Aliases
SCN1A, Na(v)1.1, FEB3, NAC1, SCN1, SMEI, HBSCI, GEFSP2, Nav1.1Associated Syndromes
Dravet syndrome, Dravet syndrome, epilepsy/seizuresChromosome Band
2q24.3Associated Disorders
DD/NDD, ADHD, ID, EP, EPS, ASDRelevance to Autism
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018). Additional de novo missense variants in the SCN1A gene were identified in novel ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; subsequent TADA analysis in this report identified SCN1A as a candidate gene with a false discovery rate < 0.1.
Molecular Function
This gene encodes the large alpha subunit of the vertebrate voltage-gated sodium channel essential for the generation and propagation of action potentials, mainly in nerve and muscle.
External Links
SFARI Genomic Platforms
Reports related to SCN1A (98 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2 | Escayg A , et al. (2000) | No | - |
| 2 | Highly Cited | De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy | Claes L , et al. (2001) | No | - |
| 3 | Primary | Sodium channels SCN1A, SCN2A and SCN3A in familial autism | Weiss LA , et al. (2003) | Yes | - |
| 4 | Support | Nonfunctional SCN1A is common in severe myoclonic epilepsy of infancy | Ohmori I , et al. (2006) | No | - |
| 5 | Recent Recommendation | Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings | Wolff M , et al. (2006) | No | - |
| 6 | Recent Recommendation | Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation | Osaka H , et al. (2007) | No | Asperger syndrome |
| 7 | Recent Recommendation | Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation | Ogiwara I , et al. (2007) | No | - |
| 8 | Support | Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations | O'Roak BJ , et al. (2011) | Yes | - |
| 9 | Support | Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy | Klassen T , et al. (2011) | No | - |
| 10 | Support | Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile seizures | Shi YW , et al. (2011) | No | - |
| 11 | Support | Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations | O'Roak BJ , et al. (2012) | Yes | - |
| 12 | Support | SCN1A mutation associated with intractable myoclonic epilepsy and migraine headache | Frosk P , et al. (2012) | No | Epilepsy, ASD |
| 13 | Support | Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome | Kwong AK , et al. (2012) | No | ASD, ID |
| 14 | Recent Recommendation | Nontruncating SCN1A mutations associated with severe myoclonic epilepsy of infancy impair cell surface expression | Thompson CH , et al. (2012) | No | - |
| 15 | Support | Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders | O'Roak BJ , et al. (2012) | Yes | - |
| 16 | Support | Generalized epilepsy with febrile seizure plus (GEFS+) spectrum: Novel de novo mutation of SCN1A detected in a Malaysian patient | Tan EH , et al. (2012) | No | DD, ID |
| 17 | Recent Recommendation | SCN1A testing for epilepsy: application in clinical practice | Hirose S , et al. (2013) | No | - |
| 18 | Support | Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 | Carvill GL , et al. (2013) | No | ID, ASD, DD |
| 19 | Positive Association | De novo mutations in epileptic encephalopathies | Epi4K Consortium , et al. (2013) | No | IS, LGS, DD, ID, ASD, ADHD |
| 20 | Support | Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations | Toma C , et al. (2013) | Yes | - |
| 21 | Positive Association | Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A | Kasperaviciute D , et al. (2013) | No | - |
| 22 | Support | Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder | Koshimizu E , et al. (2013) | Yes | ID, epilepsy |
| 23 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 24 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
| 25 | Recent Recommendation | Integrated systems analysis reveals a molecular network underlying autism spectrum disorders | Li J , et al. (2015) | Yes | - |
| 26 | Recent Recommendation | Incorporating Functional Information in Tests of Excess De Novo Mutational Load | Jiang Y , et al. (2015) | No | - |
| 27 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 28 | Support | Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities | Zhang Y , et al. (2015) | No | - |
| 29 | Support | Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms | D'Gama AM , et al. (2015) | Yes | - |
| 30 | Recent Recommendation | CRISPR/Cas9 facilitates investigation of neural circuit disease using human iPSCs: mechanism of epilepsy caused by an SCN1A loss-of-function mutation | Liu J , et al. (2016) | No | - |
| 31 | Support | Comprehensive molecular testing in patients with high functioning autism spectrum disorder | Alvarez-Mora MI , et al. (2016) | Yes | - |
| 32 | Support | The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies | Schuch JB , et al. (2016) | No | - |
| 33 | Support | A Point Mutation in SCN1A 5' Genomic Region Decreases the Promoter Activity and Is Associated with Mild Epilepsy and Seizure Aggravation Induced by Antiepileptic Drug | Gao QW , et al. (2016) | No | - |
| 34 | Support | Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy | Fry AE , et al. (2016) | No | - |
| 35 | Support | Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability | Riazuddin S , et al. (2016) | No | - |
| 36 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
| 37 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies | Redin C , et al. (2016) | No | - |
| 38 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families | Trujillano D , et al. (2016) | No | - |
| 39 | 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 | Dravet syndrome |
| 40 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
| 41 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | No | - |
| 42 | 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 | - |
| 43 | Support | Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders | Li J , et al. (2017) | Yes | - |
| 44 | Support | Expanding the genetic heterogeneity of intellectual disability | Anazi S , et al. (2017) | No | - |
| 45 | Support | High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies | Hamdan FF , et al. (2017) | No | DD/ID |
| 46 | Support | Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice | Tumien B , et al. (2017) | No | Developmental regression |
| 47 | Support | Mosaicism of de novo pathogenic SCN1A variants in epilepsy is a frequent phenomenon that correlates with variable phenotypes | de Lange IM , et al. (2018) | No | DD/ID, ASD, ADHD |
| 48 | Support | Language Regression in an Atypical SLC6A1 Mutation | Islam MP , et al. (2018) | Yes | Language delay, regression |
| 49 | Support | Clinical genome sequencing in an unbiased pediatric cohort | Thiffault I , et al. (2018) | No | DD, epilepsy/seizures |
| 50 | Support | First report on the association of SCN1A mutation, childhood schizophrenia and autism spectrum disorder without epilepsy | Papp-Hertelendi R , et al. (2018) | Yes | - |
| 51 | Recent Recommendation | Aberrant Inclusion of a Poison Exon Causes Dravet Syndrome and Related SCN1A-Associated Genetic Epilepsies | Carvill GL , et al. (2018) | No | - |
| 52 | Support | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
| 53 | Support | The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders | Jiao Q , et al. (2019) | No | ID |
| 54 | Support | Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes | Xiong J , et al. (2019) | Yes | Dravet syndrome |
| 55 | Support | Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population | Monies D , et al. (2019) | No | Autistic features, stereotypies |
| 56 | Support | Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients | Balicza P , et al. (2019) | Yes | Dravet syndrome |
| 57 | Support | The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children | Long S , et al. (2019) | Yes | - |
| 58 | Support | Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability | Borlot F , et al. (2019) | No | Autistic features |
| 59 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
| 60 | Support | Re-annotation of 191 developmental and epileptic encephalopathy-associated genes unmasks de novo variants in SCN1A | Steward CA , et al. (2019) | No | - |
| 61 | Support | Autism risk in offspring can be assessed through quantification of male sperm mosaicism | Breuss MW , et al. (2019) | Yes | - |
| 62 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 63 | Support | Utility of clinical exome sequencing in a complex Emirati pediatric cohort | Mahfouz NA et al. (2020) | No | - |
| 64 | Support | Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy | Lee J et al. (2020) | Yes | ID, epilepsy/seizures |
| 65 | Support | A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders | Suzuki T et al. (2020) | No | ASD |
| 66 | 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 | Psychomotor retardation |
| 67 | Support | Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression | Yin J et al. (2020) | Yes | Developmental regression, epilepsy/seizures |
| 68 | Support | Clinical and genetic characteristics of patients with Doose syndrome | Hinokuma N et al. (2020) | No | - |
| 69 | Support | - | Zou D et al. (2021) | No | - |
| 70 | Support | - | Pode-Shakked B et al. (2021) | No | - |
| 71 | Support | - | Mahjani B et al. (2021) | Yes | - |
| 72 | Support | - | Chen S et al. (2021) | Yes | Epilepsy/seizures |
| 73 | Support | - | Sheth H et al. (Nov-) | No | DD, ID |
| 74 | Support | - | Su T et al. (2022) | No | DD, ID |
| 75 | Support | - | Tuncay IO et al. (2022) | Yes | DD, ID, epilepsy/seizures |
| 76 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
| 77 | Support | - | Verberne EA et al. (2022) | No | - |
| 78 | Support | - | Brea-Fernández AJ et al. (2022) | No | - |
| 79 | Support | - | Kaneko K et al. (2022) | No | - |
| 80 | Support | - | Wang JY et al. (2022) | No | ID, learning disability |
| 81 | Support | - | Hieu NLT et al. (2022) | No | - |
| 82 | Support | - | Almog Y et al. (2022) | No | - |
| 83 | Support | - | Chuan Z et al. (2022) | No | ID |
| 84 | Support | - | Stenshorne I et al. (2022) | No | ASD |
| 85 | Support | - | Zhou X et al. (2022) | Yes | - |
| 86 | Support | - | Shimelis H et al. (2023) | No | - |
| 87 | Support | - | Yuan B et al. (2023) | Yes | - |
| 88 | Support | - | Hu C et al. (2023) | Yes | - |
| 89 | Support | - | van Hugte EJH et al. (2023) | No | ASD, ADHD, ID |
| 90 | Support | - | Balasar et al. (2023) | No | - |
| 91 | Support | - | Sanchis-Juan A et al. (2023) | No | ASD, DD |
| 92 | Support | - | Sheth F et al. (2023) | Yes | DD, ID |
| 93 | Support | - | et al. () | No | - |
| 94 | Support | - | et al. () | No | Autistic features |
| 95 | Support | - | et al. () | No | - |
| 96 | Support | - | et al. () | No | - |
| 97 | Support | - | et al. () | No | ASD, DD |
| 98 | Support | - | et al. () | No | - |
Rare Variants (264)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | inversion | De novo | - | - | 27841880 | Redin C , et al. (2016) | |
| - | - | copy_number_loss | De novo | - | - | 27113213 | Fry AE , et al. (2016) | |
| - | - | copy_number_loss | Unknown | - | - | 32913952 | Hinokuma N et al. (2020) | |
| c.2044-3C>G | - | splice_region_variant | Unknown | - | - | 38438125 | et al. () | |
| - | - | copy_number_loss | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.677C>T | p.Thr226Met | missense_variant | De novo | - | - | 38374498 | et al. () | |
| c.1025C>T | p.Ala342Val | missense_variant | De novo | - | - | 38256219 | et al. () | |
| c.2659G>A | p.Val887Met | missense_variant | Unknown | - | - | 38438125 | et al. () | |
| c.5252C>T | p.Ser1751Leu | missense_variant | Unknown | - | - | 37943464 | et al. () | |
| c.5087T>C | p.Phe1696Ser | missense_variant | De novo | - | - | 38374498 | et al. () | |
| c.4300T>C | p.Trp1434Arg | missense_variant | Unknown | - | - | 38438125 | et al. () | |
| c.4378T>A | p.Tyr1460Asn | missense_variant | Unknown | - | - | 38438125 | et al. () | |
| - | - | nonsynonymous_variant | Unknown | - | Unknown | 25549968 | Li J , et al. (2015) | |
| G>A | p.? | splice_site_variant | De novo | - | - | 11359211 | Claes L , et al. (2001) | |
| - | - | copy_number_loss | De novo | - | Simplex | 30526861 | Carvill GL , et al. (2018) | |
| c.602+1G>A | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1738C>T | p.Arg580Ter | stop_gained | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.1837C>T | p.Arg613Ter | stop_gained | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.383+1A>G | - | splice_site_variant | De novo | - | - | 35359575 | Wang JY et al. (2022) | |
| c.602+1G>A | - | splice_site_variant | De novo | - | - | 35359575 | Wang JY et al. (2022) | |
| c.3299insAA | - | frameshift_variant | De novo | - | - | 11359211 | Claes L , et al. (2001) | |
| c.305T>C | p.Phe102Ser | missense_variant | De novo | - | Simplex | 38328757 | et al. () | |
| c.5148C>A | p.Cys1716Ter | stop_gained | Unknown | - | - | 34800434 | Chen S et al. (2021) | |
| c.1333C>T | p.Gln445Ter | stop_gained | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.2584C>T | p.Arg862Ter | stop_gained | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.79A>C | p.Arg27= | missense_variant | De novo | - | - | 31139143 | Long S , et al. (2019) | |
| c.664C>T | p.Arg222Ter | stop_gained | De novo | - | - | 11359211 | Claes L , et al. (2001) | |
| c.4096G>A | p.Val1366Ile | missense_variant | - | - | - | 17507202 | Osaka H , et al. (2007) | |
| c.2624C>T | p.Thr875Met | missense_variant | - | - | - | 10742094 | Escayg A , et al. (2000) | |
| c.2836C>T | p.Arg946Cys | missense_variant | Unknown | - | Simplex | 38328757 | et al. () | |
| c.3733C>T | p.Arg1245Ter | stop_gained | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.3637C>T | p.Arg1213Ter | stop_gained | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.-159_-156del | - | frameshift_variant | De novo | - | - | 31139143 | Long S , et al. (2019) | |
| c.569G>A | p.Trp190Ter | stop_gained | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.4943G>A | p.Arg1648His | missense_variant | - | - | - | 10742094 | Escayg A , et al. (2000) | |
| c.5864T>C | p.Ile1955Thr | missense_variant | - | - | - | 12610651 | Weiss LA , et al. (2003) | |
| c.603-2A>G | - | splice_site_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.3969+2451G>C | - | intron_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.4786C>T | p.Arg1596Cys | missense_variant | Unknown | - | Simplex | 38328757 | et al. () | |
| c.5148C>A | p.Cys1716Ter | stop_gained | De novo | - | - | 31031587 | Xiong J , et al. (2019) | |
| c.2589+3A>T | - | intron_variant | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.1053T>A | p.Cys351Ter | stop_gained | Unknown | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.1348C>T | p.Gln450Ter | stop_gained | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.2214G>A | p.Trp738Ter | stop_gained | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.1051T>C | p.Cys351Arg | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.2576G>A | p.Arg859His | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.2585G>A | p.Arg862Gln | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.2791C>A | p.Arg931Ser | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.437C>A | p.Thr146Lys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4048G>A | p.Val1350Met | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.4852+1G>T | - | splice_site_variant | Unknown | - | Unknown | 32722525 | Yin J et al. (2020) | |
| c.1000C>G | p.Leu334Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2182G>A | p.Glu728Lys | missense_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| c.301C>T | p.Arg101Trp | missense_variant | De novo | - | - | 27113213 | Fry AE , et al. (2016) | |
| c.302G>A | p.Arg101Gln | missense_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.524C>T | p.Ala175Val | missense_variant | De novo | - | - | 31139143 | Long S , et al. (2019) | |
| c.668C>T | p.Ala223Val | missense_variant | De novo | - | - | 31139143 | Long S , et al. (2019) | |
| c.277T>C | p.Leu93= | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.2134C>T | p.Arg712Ter | stop_gained | Unknown | - | - | 35253369 | Verberne EA et al. (2022) | |
| c.5347G>A | p.Ala1783Thr | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2923C>T | p.Leu975Phe | missense_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.602+1G>A | - | splice_site_variant | De novo | - | Simplex | 34979677 | Sheth H et al. (Nov-) | |
| c.275T>G | p.Val92Gly | missense_variant | De novo | - | - | 31273778 | Borlot F , et al. (2019) | |
| c.3637C>T | p.Arg1213Ter | stop_gained | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.5197A>G | p.Ile1733Val | missense_variant | De novo | - | - | 23248692 | Tan EH , et al. (2012) | |
| c.5005G>A | p.Ala1669Thr | missense_variant | De novo | - | - | 27113213 | Fry AE , et al. (2016) | |
| c.3620T>C | p.Leu1207Pro | missense_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.5315C>G | p.Ala1772Gly | missense_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.4243T>C | p.Phe1415Leu | missense_variant | Unknown | - | - | 31139143 | Long S , et al. (2019) | |
| c.3982T>C | p.Ser1328Pro | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.3986G>T | p.Arg1329Leu | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.4310T>C | p.Ile1437Thr | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.2956C>T | p.Leu986Phe | missense_variant | De novo | - | - | 11359211 | Claes L , et al. (2001) | |
| c.311C>T | p.Ala104Val | missense_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.945G>A | p.Lys315= | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.2214dup | p.Tyr739ValfsTer2 | intron_variant | Unknown | - | - | 32477112 | Lee J et al. (2020) | |
| c.5726C>T | p.Thr1909Ile | missense_variant | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
| c.1177C>A | p.Arg393Ser | missense_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.1264G>A | p.Val422Met | missense_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.1390G>C | p.Ala464Pro | missense_variant | Unknown | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.1546G>A | p.Asp516Asn | missense_variant | Unknown | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.179A>G | p.Asn60Ser | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.4878_4880del | p.Lys1627del | inframe_indel | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.4853-25T>A | - | frameshift_variant | Familial | Maternal | - | 35359575 | Wang JY et al. (2022) | |
| c.2220A>T | p.Lys740Asn | splice_site_variant | De novo | - | - | 31139143 | Long S , et al. (2019) | |
| c.4284+2T>C | - | splice_site_variant | Familial | Paternal | - | 35359575 | Wang JY et al. (2022) | |
| c.2116G>T | p.Asp706Tyr | stop_gained | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.2134C>T | p.Arg712Ter | stop_gained | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.3641T>G | p.Ile1214Arg | missense_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.5171C>T | p.Ala1724Val | missense_variant | Unknown | - | - | 31273778 | Borlot F , et al. (2019) | |
| c.3686T>G | p.Leu1229Arg | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| c.1177C>T | p.Arg393Cys | missense_variant | De novo | - | - | 31873310 | Breuss MW , et al. (2019) | |
| c.602+1G>A | - | splice_site_variant | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
| c.650C>T | p.Thr217Ile | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.4002+2451G>C | - | intron_variant | De novo | - | Simplex | 30526861 | Carvill GL , et al. (2018) | |
| - | - | copy_number_loss | Unknown | Not maternal | Simplex | 30526861 | Carvill GL , et al. (2018) | |
| c.265-19T>C | - | intron_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.602+1G>A | - | splice_site_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.1200_1202del | p.Met400del | inframe_deletion | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.909A>G | p.Thr303%3D | splice_region_variant | De novo | - | - | 35359575 | Wang JY et al. (2022) | |
| c.3733C>T | p.Arg1245Ter | stop_gained | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.4547C>A | p.Ser1516Ter | stop_gained | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.4302G>A | p.Trp1434Ter | stop_gained | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
| c.4814A>T | p.Asn1605Ile | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.4934G>A | p.Arg1645Gln | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.4934G>A | p.Arg1645Gln | missense_variant | De novo | - | - | 31134136 | Balicza P , et al. (2019) | |
| c.664C>T | p.Arg222Ter | stop_gained | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| A>G | p.Phe408Leu | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.1852C>T | p.Arg618Cys | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.2917A>G | p.Met973Val | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.980T>G | p.Leu327Arg | missense_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.4020T>G | p.Leu1340= | missense_variant | De novo | - | - | 30008475 | Thiffault I , et al. (2018) | |
| c.5379del | p.Glu1794LysfsTer7 | frameshift_variant | Unknown | - | Simplex | 38328757 | et al. () | |
| c.427G>A | p.Val143Met | missense_variant | Familial | Maternal | - | 37007974 | Hu C et al. (2023) | |
| c.4868A>C | p.Glu1623Ala | missense_variant | De novo | - | Simplex | 35082603 | Su T et al. (2022) | |
| c.1200_1202del | p.Met400del | inframe_deletion | De novo | - | - | 35359575 | Wang JY et al. (2022) | |
| c.32C>A | p.Pro11His | missense_variant | De novo | - | Simplex | 28940097 | Anazi S , et al. (2017) | |
| c.3607C>T | p.Gln1203Ter | stop_gained | Unknown | - | Unknown | 31130284 | Monies D , et al. (2019) | |
| c.3977C>T | p.Ala1326Val | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.4033C>T | p.Pro1345Ser | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.4453A>G | p.Asn1485Asp | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.5195C>T | p.Pro1732Leu | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.79G>A | - | coding_sequence_variant | De novo | - | Simplex | 31814998 | Steward CA , et al. (2019) | |
| c.811G>A | p.Gly271Ser | missense_variant | Familial | Maternal | Multiplex | 38328757 | et al. () | |
| c.5414_5415del | p.Phe1805Ter | frameshift_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.2248T>C | p.Cys750Arg | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.3269G>C | p.Ser1090Thr | missense_variant | Unknown | - | Unknown | 32722525 | Yin J et al. (2020) | |
| c.1876A>G | p.Ser626Gly | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.5313_5315del | p.Ile1772del | inframe_deletion | De novo | - | - | 35359575 | Wang JY et al. (2022) | |
| c.505T>C | p.Ser169Pro | missense_variant | De novo | - | Simplex | 34979677 | Sheth H et al. (Nov-) | |
| c.254T>A | p.Ile85Asn | missense_variant | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.5538G>A | p.(=) | synonymous_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.4002+2168_4002+2172del | - | intron_variant | De novo | - | - | 30526861 | Carvill GL , et al. (2018) | |
| c.301G>A | - | coding_sequence_variant | De novo | - | Simplex | 31814998 | Steward CA , et al. (2019) | |
| c.2681C>G | p.Thr894Ser | missense_variant | Familial | - | - | 35979408 | Stenshorne I et al. (2022) | |
| c.4926G>C | p.Arg1642Ser | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.5348C>T | p.Ala1783Val | missense_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.4277T>C | p.Leu1426Pro | missense_variant | De novo | - | - | 35979408 | Stenshorne I et al. (2022) | |
| c.3637C>T | p.Arg1213Ter | stop_gained | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.2933T>C | p.Ile978Thr | missense_variant | Familial | Paternal | - | 34145886 | Zou D et al. (2021) | |
| c.3308T>C | p.Met1103Thr | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.5449C>T | p.Pro1817Ser | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.1132del | p.Leu378Ter | frameshift_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.602+1G>A | - | splice_site_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.2118del | p.Pro707LeufsTer8 | frameshift_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.1693dup | p.Ser565PhefsTer6 | frameshift_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.5351T>A | p.Val1784Asp | missense_variant | De novo | - | Simplex | 34979677 | Sheth H et al. (Nov-) | |
| c.1171A>C | p.Thr391Pro | missense_variant | De novo | - | Simplex | 32530565 | Suzuki T et al. (2020) | |
| c.1A>C | p.Met1? | initiator_codon_variant | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
| c.310G>C | p.Ala104Pro | missense_variant | De novo | - | Simplex | 31130284 | Monies D , et al. (2019) | |
| c.677C>T | p.Thr226Met | missense_variant | Unknown | - | Unknown | 31130284 | Monies D , et al. (2019) | |
| c.4002+2455G>A | - | intron_variant | Unknown | Not maternal | - | 30526861 | Carvill GL , et al. (2018) | |
| c.3705+5G>A | - | splice_site_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.2101C>T | p.Arg701Ter | stop_gained | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
| c.3412del | p.Leu1138TrpfsTer8 | frameshift_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.4942C>T | p.Arg1648Cys | missense_variant | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| c.4048G>A | p.Val1350Met | missense_variant | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
| c.4439G>T | p.Gly1480Val | missense_variant | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
| c.5341T>C | p.Tyr1781His | missense_variant | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
| c.2824C>G | p.Leu942Val | missense_variant | Unknown | - | Unknown | 31130284 | Monies D , et al. (2019) | |
| c.5797C>T | p.Arg1933Ter | stop_gained | Familial | Paternal | - | 31452935 | Feliciano P et al. (2019) | |
| c.4834G>A | p.Val1612Ile | missense_variant | Familial | Maternal | - | 27824329 | Wang T , et al. (2016) | |
| c.5111T>C | p.Ile1704Thr | missense_variant | Familial | Maternal | - | 30945278 | Jiao Q , et al. (2019) | |
| c.5161A>T | p.Thr1721Ser | missense_variant | Familial | Paternal | - | 30945278 | Jiao Q , et al. (2019) | |
| c.2722G>A | p.Gly908Ser | missense_variant | Unknown | - | Multiplex | 37524782 | Balasar et al. (2023) | |
| NM_001165963:IVS3+3A>C | p.? | splice_site_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.3587T>C | p.Leu1196Pro | missense_variant | Unknown | - | Unknown | 31130284 | Monies D , et al. (2019) | |
| c.1006T>G | p.Cys336Gly | missense_variant | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.2134C>T | p.Arg712Ter | stop_gained | De novo | - | Simplex | 32651551 | van der Werf IM et al. (2020) | |
| c.4319C>T | p.Ala1440Val | missense_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.1177C>T | p.Arg393Cys | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.2876G>A | p.Cys959Tyr | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.4096G>A | p.Val1366Ile | missense_variant | Familial | Maternal | - | 17507202 | Osaka H , et al. (2007) | |
| c.253_254del | p.Ile85GlnfsTer2 | frameshift_variant | De novo | - | - | 11359211 | Claes L , et al. (2001) | |
| c.2378C>T | p.Thr793Met | missense_variant | Familial | Maternal | - | 22848613 | Kwong AK , et al. (2012) | |
| c.1757C>T | p.Ser586Phe | missense_variant | Familial | Paternal | - | 29961511 | Islam MP , et al. (2018) | |
| c.4229del | p.Asn1410MetfsTer2 | frameshift_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| NM_001165963:IVS21+1G>A | p.? | splice_site_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.5714C>T | p.Pro1905Leu | missense_variant | De novo | - | Simplex | 21572417 | O'Roak BJ , et al. (2011) | |
| c.5314G>A | p.Ala1772Thr | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.5315C>T | p.Ala1772Val | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.5714C>T | p.Pro1905Leu | missense_variant | De novo | - | Simplex | 22495309 | O'Roak BJ , et al. (2012) | |
| c.5779C>T | p.Arg1927Gly | missense_variant | De novo | - | Simplex | 23160955 | O'Roak BJ , et al. (2012) | |
| c.4698T>C | p.Ser1566= | synonymous_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.4529C>A | p.Ala1510Glu | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.5222G>C | p.Cys1741Ser | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.2189T>G;c.2097T>G | - | 2KB_upstream_variant | Familial | Maternal | - | 26969601 | Gao QW , et al. (2016) | |
| c.4834G>A | p.Val1612Ile | missense_variant | Familial | Maternal | - | 22848613 | Kwong AK , et al. (2012) | |
| c.4558del | p.Gln1520LysfsTer19 | frameshift_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.5962del | p.Arg1988GlyfsTer2 | frameshift_variant | Unknown | - | - | 36475376 | Shimelis H et al. (2023) | |
| c.5536_5539del | p.Lys1846SerfsTer11 | frameshift_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.3493_3495del | p.Glu1165del | inframe_deletion | Unknown | - | Simplex | 37543562 | Sheth F et al. (2023) | |
| c.3320dup | p.Asn1107LysfsTer17 | frameshift_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.1209del | p.Phe403LeufsTer12 | frameshift_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.4836del | p.Ile1613PhefsTer5 | frameshift_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.3672del | p.Ile1224MetfsTer4 | frameshift_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.587del | p.Thr196MetfsTer20 | frameshift_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.4612G>A | p.Val1538Ile | missense_variant | Unknown | - | Unknown | 24066114 | Koshimizu E , et al. (2013) | |
| c.1261G>A | p.Val421Met | missense_variant | De novo | - | Simplex | 27848944 | Trujillano D , et al. (2016) | |
| c.2576G>A | p.Arg859His | missense_variant | Unknown | - | Unknown | 37467479 | van Hugte EJH et al. (2023) | |
| c.677C>T | p.Thr226Met | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.1150T>G | p.Trp384Gly | missense_variant | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
| c.3402_3403del | p.Ser1134ArgfsTer13 | frameshift_variant | De novo | - | - | 34800434 | Chen S et al. (2021) | |
| c.5536_5539del | p.Lys1846SerfsTer11 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2729A>G | p.Gln910Arg | missense_variant | Unknown | Not maternal | - | 31273778 | Borlot F , et al. (2019) | |
| c.200_203del | p.Asp67ValfsTer24 | splice_site_variant | De novo | - | - | 29286531 | Tumien B , et al. (2017) | |
| c.568T>C | p.Trp190Arg | missense_variant | Unknown | Not maternal | - | 27864847 | Parrini E , et al. (2016) | |
| c.4757del | p.Gly1586GlufsTer5 | frameshift_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.4168G>A | p.Val1390Met | missense_variant | Unknown | - | Unknown | 37467479 | van Hugte EJH et al. (2023) | |
| c.1876A>G | p.Ser626Gly | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.5103_5106del | p.Ile1701MetfsTer13 | frameshift_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.285_286insAGAA | p.Gly96ArgfsTer24 | frameshift_variant | De novo | - | - | 27113213 | Fry AE , et al. (2016) | |
| c.5119_5122del | p.Phe1707ArgfsTer7 | frameshift_variant | De novo | - | - | 11359211 | Claes L , et al. (2001) | |
| c.218_252del | p.Val73AspfsTer3 | frameshift_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.5503C>T | p.Leu1835Phe | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.5300T>A | p.Val1767Asp | missense_variant | De novo | - | Simplex | 34580403 | Pode-Shakked B et al. (2021) | |
| c.4970G>A | p.Arg1657His | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.4868A>C | p.Glu1623Ala | missense_variant | Familial | Maternal | Multiplex | 35082603 | Su T et al. (2022) | |
| c.3931G>A | p.Ala1311Thr | missense_variant | Familial | Paternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.4834G>A | p.Val1612Ile | missense_variant | Familial | Maternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.4574_4577del | p.Arg1525GlnfsTer13 | frameshift_variant | De novo | - | - | 11359211 | Claes L , et al. (2001) | |
| c.3402_3403del | p.Ser1134ArgfsTer13 | frameshift_variant | De novo | - | - | 31031587 | Xiong J , et al. (2019) | |
| c.4481G>A | p.Gly1494Glu | missense_variant | De novo | - | Simplex | 32651551 | van der Werf IM et al. (2020) | |
| c.3000del | p.Ala1001GlnfsTer9 | frameshift_variant | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
| NM_001202435.3:c.3430_3C>G | p.? | splice_site_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.3521C>G | p.Thr1174Ser | missense_variant | Familial | Maternal | Simplex | 22550089 | Frosk P , et al. (2012) | |
| c.4061del | p.Cys1354PhefsTer6 | frameshift_variant | Unknown | - | Unknown | 31130284 | Monies D , et al. (2019) | |
| c.4384_4385del | p.Tyr1462LeufsTer23 | frameshift_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.983_984insC | p.Glu328AspfsTer12 | frameshift_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.4411T>C | p.Ser1471Pro | missense_variant | Familial | Paternal | Multiplex | 22151702 | Shi YW , et al. (2011) | |
| c.3497A>C | p.Gln1166Pro | missense_variant | Familial | Paternal | Multiplex | 23999528 | Toma C , et al. (2013) | |
| c.2971_2972delinsG | p.Leu991ValfsTer2 | frameshift_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
| c.1076A>C | p.Asn359Thr | missense_variant | Familial | Unknown | Unknown | 23708187 | Carvill GL , et al. (2013) | |
| c.4793A>T | p.Tyr1598Phe | missense_variant | Unknown | - | Simplex | 30060894 | Papp-Hertelendi R , et al. (2018) | |
| c.1625G>A | p.Arg542Gln | missense_variant | Familial | Paternal | Multiplex | 12610651 | Weiss LA , et al. (2003) | |
| c.3890_3903del | p.Val1297GlufsTer30 | frameshift_variant | De novo | - | - | 29460957 | de Lange IM , et al. (2018) | |
| c.3905dup | p.Asn1302LysfsTer30 | frameshift_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
| c.3101T>C | p.Ile1034Thr | missense_variant | Familial | Paternal | Multiplex | 12610651 | Weiss LA , et al. (2003) | |
| c.3112T>C | p.Phe1038Leu | missense_variant | Familial | Paternal | Multiplex | 12610651 | Weiss LA , et al. (2003) | |
| c.5488_5489del | p.Gln1830ValfsTer6 | frameshift_variant | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
| c.4002+2165C>T | - | intron_variant | Familial | Paternal | Multi-generational | 30526861 | Carvill GL , et al. (2018) | |
| c.4002+2503C>T | - | intron_variant | Familial | Maternal | Multi-generational | 30526861 | Carvill GL , et al. (2018) | |
| c.3562delinsCC | p.Arg1188ProfsTer29 | frameshift_variant | Familial | Paternal | - | 30945278 | Jiao Q , et al. (2019) | |
| c.5370_5373del | p.Ser1790ArgfsTer10 | frameshift_variant | De novo | - | Simplex | 35190550 | Tuncay IO et al. (2022) | |
| c.4554dup | p.Pro1519ThrfsTer18 | frameshift_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.248A>G | p.Tyr83Cys | missense_variant | Familial | Maternal | Multi-generational | 30945278 | Jiao Q , et al. (2019) | |
| c.4553_4554del | p.Lys1518ThrfsTer18 | frameshift_variant | De novo | - | Multiplex | 32530565 | Suzuki T et al. (2020) | |
| c.3926T>G | p.Leu1309Arg | missense_variant | Familial | Paternal | Multiplex | 37467479 | van Hugte EJH et al. (2023) | |
| c.1811G>A | p.Arg604His | missense_variant | Familial | Maternal | Simplex | 26845707 | Alvarez-Mora MI , et al. (2016) | |
| c.393C>G | p.Ser131Arg | missense_variant | Familial | Maternal | Multi-generational | 27113213 | Fry AE , et al. (2016) | |
| c.5768A>G | p.Gln1923Arg | missense_variant | Familial | Paternal | Multi-generational | 22151702 | Shi YW , et al. (2011) | |
| c.5010_5013del | p.Phe1671ThrfsTer8 | frameshift_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.133G>A | p.Asp45Asn | missense_variant | Familial | Paternal | Multi-generational | 23708187 | Carvill GL , et al. (2013) | |
| c.1848G>C | p.Glu616Asp | missense_variant | Familial | Maternal | Multi-generational | 27864847 | Parrini E , et al. (2016) | |
| c.5513C>T | p.Pro1838Leu | missense_variant | De novo | - | Multiplex (monozygotic twins) | 35365919 | Hieu NLT et al. (2022) | |
| c.2862+1G>T;c.2913+1G>T;c.2946+1G>T | p.? | splice_site_variant | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.5732T>G | p.Ile1911Ser | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.5119_5122del | p.Phe1707ArgfsTer7 | frameshift_variant | Unknown | - | Extended multiplex | 32382396 | Mahfouz NA et al. (2020) | |
| c.4319C>T | p.Pro1440Leu | missense_variant | Unknown | - | Multiplex or multi-generational | 26637798 | D'Gama AM , et al. (2015) | |
| c.5501C>T | p.Ala1834Val | missense_variant | Familial | Both parents | Extended multiplex | 27457812 | Riazuddin S , et al. (2016) | |
| c.5962C>T | p.Arg1988Trp | missense_variant | Familial | Paternal and maternal | Multi-generational | 23708187 | Carvill GL , et al. (2013) | |
| c.2050C>T;c.2101C>T;c.2134C>T | p.Arg684Ter;p.Arg701Ter;p.Arg712Ter | stop_gained | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.2629G>C;c.2680G>C;c.2713G>C | p.Ala877Pro;p.Ala894Pro;p.Ala905Pro | missense_variant | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.5234C>A;c.5285C>A;c.5318C>A | p.Ser1745Tyr;p.Ser1762Tyr;p.Ser1773Tyr | missense_variant | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) |
Common Variants (2)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.264+3440A>G | - | intron_variant | - | - | - | 24014518 | Kasperaviciute D , et al. (2013) | |
| c.-142+26807G>T | Minor allele, A | intron_variant | - | - | - | 24014518 | Kasperaviciute D , et al. (2013) |
SFARI Gene score
High Confidence, Syndromic
Score Delta: Score remained at 1S
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.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
10/1/2020
Score remained at 1
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018).
7/1/2020
Score remained at 1
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018).
Reports Added
[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020] [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]4/1/2020
Score remained at 1
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018).
1/1/2020
Score remained at 1
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018).
Reports Added
[Re-annotation of 191 developmental and epileptic encephalopathy-associated genes unmasks de novo variants in SCN1A.2019] [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]10/1/2019
Decreased from 3S to 1
New Scoring Scheme
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018).
7/1/2019
Decreased from 3S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018).
Reports Added
[Nonfunctional SCN1A is common in severe myoclonic epilepsy of infancy.2006] [Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients.2019] [The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children.2019] [Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability.2019]4/1/2019
Decreased from 3S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017)
1/1/2019
Decreased from 3S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017)
10/1/2018
Decreased from 3S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017)
7/1/2018
Decreased from 3S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017)
10/1/2017
Decreased from 3S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017)
Reports Added
[Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.2017] [Expanding the genetic heterogeneity of intellectual disability.2017] [High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.2017]7/1/2017
Decreased from 3S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017)
4/1/2017
Increased from S to 3S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017)
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [SCN1A mutation associated with intractable myoclonic epilepsy and migraine headache.2012] [Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS.2000] [De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy.2001] [Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation.2007] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.2012] [Generalized epilepsy with febrile seizure plus (GEFS) spectrum: Novel de novo mutation of SCN1A detected in a Malaysian patient.2012] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.2013] [Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings.2006] [Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mu...2007] [Nontruncating SCN1A mutations associated with severe myoclonic epilepsy of infancy impair cell surface expression.2012] [SCN1A testing for epilepsy: application in clinical practice.2013] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile seizures.2011] [CRISPR/Cas9 facilitates investigation of neural circuit disease using human iPSCs: mechanism of epilepsy caused by an SCN1A loss-of-function mutation.2016] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies.2016] [A Point Mutation in SCN1A 5' Genomic Region Decreases the Promoter Activity and Is Associated with Mild Epilepsy and Seizure Aggravation Induced by...2016] [Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy.2016] [Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]1/1/2017
Increased from S to S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.).
10/1/2016
Increased from S to S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.).
7/1/2016
Increased from S to S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.).
4/1/2016
Increased from S to S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.).
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [SCN1A mutation associated with intractable myoclonic epilepsy and migraine headache.2012] [Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS.2000] [De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy.2001] [Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation.2007] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.2012] [Generalized epilepsy with febrile seizure plus (GEFS) spectrum: Novel de novo mutation of SCN1A detected in a Malaysian patient.2012] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.2013] [Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings.2006] [Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mu...2007] [Nontruncating SCN1A mutations associated with severe myoclonic epilepsy of infancy impair cell surface expression.2012] [SCN1A testing for epilepsy: application in clinical practice.2013] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile seizures.2011] [CRISPR/Cas9 facilitates investigation of neural circuit disease using human iPSCs: mechanism of epilepsy caused by an SCN1A loss-of-function mutation.2016] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies.2016] [A Point Mutation in SCN1A 5' Genomic Region Decreases the Promoter Activity and Is Associated with Mild Epilepsy and Seizure Aggravation Induced by...2016] [Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy.2016]1/1/2016
Increased from S to S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.).
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [SCN1A mutation associated with intractable myoclonic epilepsy and migraine headache.2012] [Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS.2000] [De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy.2001] [Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation.2007] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.2012] [Generalized epilepsy with febrile seizure plus (GEFS) spectrum: Novel de novo mutation of SCN1A detected in a Malaysian patient.2012] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.2013] [Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings.2006] [Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mu...2007] [Nontruncating SCN1A mutations associated with severe myoclonic epilepsy of infancy impair cell surface expression.2012] [SCN1A testing for epilepsy: application in clinical practice.2013] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile seizures.2011] [CRISPR/Cas9 facilitates investigation of neural circuit disease using human iPSCs: mechanism of epilepsy caused by an SCN1A loss-of-function mutation.2016] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies.2016]7/1/2015
Increased from S to S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.).
Reports Added
[Sodium channels SCN1A, SCN2A and SCN3A in familial autism.2003] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [SCN1A mutation associated with intractable myoclonic epilepsy and migraine headache.2012] [Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS.2000] [De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy.2001] [Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation.2007] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.2012] [Generalized epilepsy with febrile seizure plus (GEFS) spectrum: Novel de novo mutation of SCN1A detected in a Malaysian patient.2012] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [De novo mutations in epileptic encephalopathies.2013] [Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.2013] [Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings.2006] [Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mu...2007] [Nontruncating SCN1A mutations associated with severe myoclonic epilepsy of infancy impair cell surface expression.2012] [SCN1A testing for epilepsy: application in clinical practice.2013] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015]1/1/2015
Increased from S to S
Description
Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.).
Krishnan Probability Score
Score 0.50669698524454
Ranking 1880/25841 scored genes
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ExAC Score
Score 0.99999999953539
Ranking 87/18225 scored genes
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Iossifov Probability Score
Score 0.957
Ranking 76/239 scored genes
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Sanders TADA Score
Score 0.12693194285863
Ranking 76/18665 scored genes
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Zhang D Score
Score 0.11455033178404
Ranking 5831/20870 scored genes
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