SYNGAP1synaptic Ras GTPase activating protein 1
Autism Reports / Total Reports
36 / 107Rare Variants / Common Variants
286 / 0Aliases
SYNGAP1, MRD5, RASA1, RASA5, SYNGAPAssociated Syndromes
Pediatric Acute-Onset Neuropsychiatric Syndrome (PChromosome Band
6p21.32Associated Disorders
DD/NDD, ADHD, ID, EP, EPS, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalRelevance to Autism
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. 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 SYNGAP1 as a gene reaching exome-wide significance (P < 2.5E-06).
Molecular Function
A major component of the postsynaptic density (PSD)associated with NMDA receptors
External Links
SFARI Genomic Platforms
Reports related to SYNGAP1 (107 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking | Kim MJ , et al. (2005) | No | - |
| 2 | Highly Cited | Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number | Flavell SW , et al. (2006) | No | - |
| 3 | Highly Cited | SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons | Rumbaugh G , et al. (2006) | No | - |
| 4 | Recent Recommendation | Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation | Hamdan FF , et al. (2009) | No | - |
| 5 | Recent Recommendation | Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP | Muhia M , et al. (2010) | No | - |
| 6 | Support | Functional impact of global rare copy number variation in autism spectrum disorders | Pinto D , et al. (2010) | Yes | - |
| 7 | Recent Recommendation | A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation | Krepischi AC , et al. (2010) | No | - |
| 8 | Support | A de novo paradigm for mental retardation | Vissers LE , et al. (2010) | No | - |
| 9 | Primary | De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism | Hamdan FF , et al. (2011) | Yes | epilepsy |
| 10 | Recent Recommendation | Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability | Hamdan FF , et al. (2011) | No | - |
| 11 | Recent Recommendation | Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory | Lee KJ , et al. (2011) | No | - |
| 12 | 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 |
| 13 | Support | Diagnostic exome sequencing in persons with severe intellectual disability | de Ligt J , et al. (2012) | No | Epilepsy, ASD |
| 14 | Recent Recommendation | Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency | Berryer MH , et al. (2012) | No | ASD, Epilepsy |
| 15 | Support | 6p21.3 microdeletion involving the SYNGAP1 gene in a patient with intellectual disability, seizures, and severe speech impairment | Writzl K and Knegt AC (2013) | No | Epilepsy |
| 16 | Recent Recommendation | Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 | Carvill GL , et al. (2013) | No | ID, ASD, DD |
| 17 | Recent Recommendation | SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity | Clement JP , et al. (2013) | No | - |
| 18 | Support | Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism | Willsey AJ , et al. (2013) | Yes | - |
| 19 | Recent Recommendation | SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks | Wang CC , et al. (2014) | No | - |
| 20 | Support | Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel | Brett M , et al. (2014) | Yes | MCA |
| 21 | Support | Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing | Redin C , et al. (2014) | No | - |
| 22 | Recent Recommendation | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 23 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 24 | Support | Recurrent de novo mutations implicate novel genes underlying simplex autism risk | O'Roak BJ , et al. (2014) | Yes | - |
| 25 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
| 26 | Recent Recommendation | Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruptions of brain morphogenesis | Kozol RA , et al. (2015) | No | - |
| 27 | Recent Recommendation | De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability | Parker MJ , et al. (2015) | No | ASD, epilepsy/seizures |
| 28 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 29 | Support | Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci | Sanders SJ , et al. (2015) | Yes | - |
| 30 | Support | Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities | Zhang Y , et al. (2015) | No | - |
| 31 | Support | Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy | Mignot C , et al. (2016) | No | ASD |
| 32 | Support | Identification of Intellectual Disability Genes in Female Patients with a Skewed X-Inactivation Pattern | Fieremans N , et al. (2016) | No | - |
| 33 | Support | Mutations in HECW2 are associated with intellectual disability and epilepsy | Halvardson J , et al. (2016) | Yes | - |
| 34 | Support | Genome-wide characteristics of de novo mutations in autism | Yuen RK et al. (2016) | Yes | - |
| 35 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
| 36 | 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 | ASD, cognitive impairment |
| 37 | Support | A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology | Vissers LE , et al. (2017) | No | - |
| 38 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | Yes | - |
| 39 | Support | Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report | Prchalova D , et al. (2017) | No | Microcephaly, growth delay, behavioral problems, s |
| 40 | 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 | ASD, epilepsy/seizures |
| 41 | Support | High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies | Hamdan FF , et al. (2017) | No | DD/ID |
| 42 | Support | Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice | Tumien B , et al. (2017) | No | - |
| 43 | Support | Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder | Takata A , et al. (2018) | Yes | - |
| 44 | Support | Novel SYNGAP1 variant in a patient with intellectual disability and distinctive dysmorphisms | Kimura Y , et al. (2018) | Yes | - |
| 45 | Support | Diagnostic value of partial exome sequencing in developmental disorders | Gieldon L , et al. (2018) | No | Microcephaly |
| 46 | Recent Recommendation | SYNGAP1 heterozygosity disrupts sensory processing by reducing touch-related activity within somatosensory cortex circuits | Michaelson SD , et al. (2018) | No | - |
| 47 | Recent Recommendation | SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy | Vlaskamp DRM , et al. (2018) | No | ASD |
| 48 | Support | - | Brimble E et al. (2019) | No | - |
| 49 | Support | Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders | Schluth-Bolard C , et al. (2019) | No | Behavioral abnormalities |
| 50 | 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 | DD |
| 51 | Support | Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes | Xiong J , et al. (2019) | Yes | ID |
| 52 | Support | Characterization of intellectual disability and autism comorbidity through gene panel sequencing | Aspromonte MC , et al. (2019) | Yes | - |
| 53 | Support | Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans | Wong WR , et al. (2019) | Yes | - |
| 54 | Support | Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression | Jimenez-Gomez A , et al. (2019) | No | ASD |
| 55 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
| 56 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 57 | 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 |
| 58 | Support | Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures | Tang S et al. (2020) | Yes | ADHD |
| 59 | Support | Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy | Lee J et al. (2020) | Yes | ID, epilepsy/seizures |
| 60 | Support | SYNGAP1 Controls the Maturation of Dendrites, Synaptic Function, and Network Activity in Developing Human Neurons | Llamosas N et al. (2020) | No | - |
| 61 | Recent Recommendation | - | Meili F et al. (2021) | Yes | - |
| 62 | Support | - | Rodin RE et al. (2021) | Yes | - |
| 63 | Support | - | Hiraide T et al. (2021) | No | - |
| 64 | Support | - | Zou D et al. (2021) | No | - |
| 65 | Support | - | Valentino F et al. (2021) | Yes | - |
| 66 | Support | - | Llamosas N et al. (2021) | Yes | - |
| 67 | Support | - | Pode-Shakked B et al. (2021) | No | - |
| 68 | Support | - | Mahjani B et al. (2021) | Yes | - |
| 69 | Support | - | Aguilera C et al. (2021) | No | Stereotypy |
| 70 | Support | - | Chen S et al. (2021) | Yes | Epilepsy/seizures |
| 71 | Support | - | Bruno LP et al. (2021) | No | Stereotypy |
| 72 | Support | - | Li D et al. (2022) | Yes | - |
| 73 | Support | - | Sheth H et al. (Nov-) | No | - |
| 74 | Support | - | Rhine CL et al. (2022) | Yes | - |
| 75 | Support | - | Brea-Fernández AJ et al. (2022) | No | - |
| 76 | Support | - | Leite AJDC et al. (2022) | No | - |
| 77 | Support | - | Kilinc M et al. (2022) | No | - |
| 78 | Support | - | Chuan Z et al. (2022) | No | DD, ID |
| 79 | Support | - | Wright D et al. (2022) | No | ASD, epilepsy/seizures |
| 80 | Support | - | Trifiletti R et al. (2022) | No | - |
| 81 | Support | - | Stenshorne I et al. (2022) | Yes | - |
| 82 | Support | - | Zhou X et al. (2022) | Yes | - |
| 83 | Support | - | Buller-Peralta I et al. (2022) | No | - |
| 84 | Support | - | Wang Y et al. (2022) | No | ASD, epilepsy/seizures |
| 85 | Support | - | Yuan B et al. (2023) | Yes | - |
| 86 | Support | - | Khlaifia A et al. (2023) | No | - |
| 87 | Recent Recommendation | - | Dawicki-McKenna JM et al. (2023) | No | - |
| 88 | Support | - | Wang J et al. (2023) | Yes | - |
| 89 | Support | - | Kipkemoi P et al. (2023) | No | Stereotypy |
| 90 | Support | - | Sanchis-Juan A et al. (2023) | No | - |
| 91 | Support | - | Ko YJ et al. (2023) | No | - |
| 92 | Recent Recommendation | - | Araki Y et al. (2023) | No | DD, ID, epilepsy/seizures |
| 93 | Support | - | Giulia Rosti et al. (2023) | No | Stereotypy |
| 94 | Support | - | Boxuan Li et al. (2023) | No | - |
| 95 | Support | - | Karthika Ajit Valaparambil et al. () | No | ASD, ADHD, epilepsy/seizures |
| 96 | Recent Recommendation | - | Marcella Birtele et al. (2023) | Yes | - |
| 97 | Recent Recommendation | - | Yoichi Araki et al. (2024) | No | - |
| 98 | Support | - | Tamam Khalaf et al. (2024) | No | ASD, ADHD, stereotypy |
| 99 | Support | - | Kimberly Wiltrout et al. (2024) | No | ASD, epilepsy/seizures |
| 100 | Support | - | Juliana Ribeiro-Constante et al. (2024) | No | ASD or autistic features |
| 101 | Support | - | Hye Jin Kim et al. () | No | Autistic features |
| 102 | Support | - | M P Kranak et al. () | No | ASD, ADHD |
| 103 | Support | - | Axel Schmidt et al. (2024) | No | Epilepsy/seizures |
| 104 | Support | - | Ben Vermaercke et al. (2024) | Yes | - |
| 105 | Support | - | Nadja Bednarczuk et al. (2024) | No | ASD, ADHD, epilepsy/seizures |
| 106 | Highly Cited | SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family | Kim JH , et al. (1998) | No | - |
| 107 | Highly Cited | A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II | Chen HJ , et al. (1998) | No | - |
Rare Variants (286)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | translocation | De novo | - | - | 30923172 | Schluth-Bolard C , et al. (2019) | |
| - | - | copy_number_loss | De novo | - | Simplex | 20531469 | Pinto D , et al. (2010) | |
| - | - | copy_number_loss | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| - | - | copy_number_loss | De novo | - | Simplex | 26079862 | Parker MJ , et al. (2015) | |
| - | p.Trp267Ter | stop_gained | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.190-2A>G | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.490C>T | p.Arg164Ter | stop_gained | De novo | - | - | 34800434 | Chen S et al. (2021) | |
| c.674C>G | p.Ser225Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.712G>T | p.Glu238Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3583-1G>A | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | - | copy_number_loss | De novo | - | Simplex | 20683986 | Krepischi AC , et al. (2010) | |
| - | - | copy_number_loss | Unknown | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2620C>T | p.Gln874Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.840C>G | p.Tyr280Ter | stop_gained | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
| c.599T>A | p.Leu200Ter | stop_gained | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
| c.2115+1G>C | - | splice_site_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
| c.3370G>T | p.Gly1124Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.490C>T | p.Arg164Ter | stop_gained | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
| c.490C>T | p.Arg164Ter | stop_gained | De novo | - | - | 31031587 | Xiong J , et al. (2019) | |
| c.3583-9G>A | - | splice_site_variant | De novo | - | - | 30800045 | Brimble E et al. (2019) | |
| c.763-1G>A | - | splice_site_variant | De novo | - | - | 30091983 | Gieldon L , et al. (2018) | |
| c.1335G>C | p.Glu445Asp | missense_variant | Unknown | - | - | 34968013 | Li D et al. (2022) | |
| c.980T>C | p.Leu327Pro | missense_variant | Unknown | - | - | 32477112 | Lee J et al. (2020) | |
| c.3190C>T | p.Gln1064Ter | stop_gained | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
| c.663+2T>C | - | splice_site_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
| c.3254G>T | p.Arg1085Leu | missense_variant | Unknown | - | - | 34968013 | Li D et al. (2022) | |
| c.1543C>T | p.Arg515Cys | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.458C>A | p.Thr153Asn | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.51C>T | p.Ser17%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1861C>T | p.Arg621Ter | stop_gained | De novo | - | - | 34653234 | Aguilera C et al. (2021) | |
| c.2059C>T | p.Arg687Ter | stop_gained | De novo | - | - | 35390071 | Leite AJDC et al. (2022) | |
| c.427C>T | p.Arg143Ter | stop_gained | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.1676+2T>C | - | splice_site_variant | De novo | - | - | 28333917 | Vissers LE , et al. (2017) | |
| c.3583-6G>A | - | splice_site_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.2337-1G>A | - | splice_site_variant | De novo | - | - | 34356170 | Valentino F et al. (2021) | |
| - | - | copy_number_loss | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.3168G>T | p.Arg1056Ser | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
| c.1030G>A | p.Gly344Ser | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1717C>T | p.Arg573Trp | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.664-2A>G | - | splice_site_variant | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.2104C>T | p.Gln702Ter | stop_gained | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.1676+5G>A | - | splice_site_variant | De novo | - | - | 28576131 | Prchalova D , et al. (2017) | |
| c.3494C>T | p.Ser1165Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4006G>A | p.Glu1336Lys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.427C>T | p.Arg143Ter | stop_gained | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.389-2A>T | p.? | splice_site_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.2782C>T | p.Gln928Ter | stop_gained | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.1908T>C | p.Phe636%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2722C>T | p.Gln908Ter | stop_gained | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.2059C>T | p.Arg687Ter | stop_gained | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.2620C>T | p.Gln874Ter | stop_gained | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.2764C>T | p.Arg922Ter | stop_gained | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.2857C>T | p.Arg953Ter | stop_gained | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.403C>T | p.Arg135Ter | stop_gained | De novo | - | Simplex | 34979677 | Sheth H et al. (Nov-) | |
| c.712G>T | p.Glu238Ter | stop_gained | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.725G>A | p.Trp242Ter | stop_gained | Unknown | - | Unknown | 38563110 | Hye Jin Kim et al. () | |
| c.2116-1G>A | - | splice_site_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.3535A>T | p.Lys1179Ter | stop_gained | Unknown | - | - | 35773312 | Trifiletti R et al. (2022) | |
| c.2794T>C | p.Phe932Leu | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| c.509+1G>T | - | splice_site_variant | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.664-2A>G | - | splice_site_variant | De novo | - | Simplex | 37928246 | Boxuan Li et al. (2023) | |
| c.509G>A | p.Arg170Gln | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.583G>C | p.Ala195Pro | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
| c.2899C>T | p.Arg967Ter | stop_gained | De novo | - | - | 31209962 | Aspromonte MC , et al. (2019) | |
| c.3718C>T | p.Arg1240Ter | stop_gained | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.3583-6G>A | - | splice_region_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.3541-12G>A | - | splice_site_variant | De novo | - | Simplex | 25167861 | Redin C , et al. (2014) | |
| c.3657_3658del | p.Tyr1219Ter | stop_gained | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| c.403C>T | p.Arg135Ter | stop_gained | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.427C>T | p.Arg143Ter | stop_gained | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.490C>T | p.Arg164Ter | stop_gained | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.403C>T | p.Arg135Ter | stop_gained | De novo | - | Simplex | 33644862 | Hiraide T et al. (2021) | |
| c.3366+1G>A | - | splice_site_variant | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.510-1G>A | - | splice_site_variant | De novo | - | Simplex | 23033978 | de Ligt J , et al. (2012) | |
| c.427C>T | p.Arg143Ter | stop_gained | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.1750_1752del | p.Ile584del | inframe_deletion | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3670C>T | p.Leu1224%3D | stop_gained | De novo | - | Simplex | 34948243 | Bruno LP et al. (2021) | |
| c.1630C>T | p.Arg544Ter | stop_gained | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.1995T>A | p.Tyr665Ter | stop_gained | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.2197C>T | p.Gln733Ter | stop_gained | De novo | - | Simplex | 29346770 | Takata A , et al. (2018) | |
| c.412A>T | p.Lys138Ter | stop_gained | De novo | - | Simplex | 19196676 | Hamdan FF , et al. (2009) | |
| c.412A>T | p.Lys138Ter | stop_gained | De novo | - | Simplex | 21376300 | Hamdan FF , et al. (2011) | |
| c.2294+1G>A | - | splice_site_variant | De novo | - | Simplex | 21237447 | Hamdan FF , et al. (2011) | |
| c.3795-1G>A | - | splice_site_variant | De novo | - | Simplex | 37463579 | Kipkemoi P et al. (2023) | |
| - | p.Lys108ValfsTer25 | frameshift_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
| c.509G>A | p.Arg170Gln | missense_variant | De novo | - | - | 35979408 | Stenshorne I et al. (2022) | |
| c.509G>A | p.Arg170Gln | missense_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| - | - | copy_number_loss | Apparently de novo | - | Simplex | 23687080 | Writzl K and Knegt AC (2013) | |
| - | - | copy_number_loss | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1744G>T | p.Glu582Ter | stop_gained | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.1861C>T | p.Arg621Ter | stop_gained | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.2899C>T | p.Arg967Ter | stop_gained | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.1513T>C | p.Tyr505His | missense_variant | De novo | - | Simplex | 37645600 | Ko YJ et al. (2023) | |
| c.1677-1G>C | - | splice_site_variant | Unknown | Not maternal | - | 36583017 | Wang Y et al. (2022) | |
| c.1735C>T | p.Arg579Ter | stop_gained | De novo | - | Simplex | 19196676 | Hamdan FF , et al. (2009) | |
| c.1735C>T | p.Arg579Ter | stop_gained | De novo | - | Simplex | 21376300 | Hamdan FF , et al. (2011) | |
| c.2050G>A | p.Asp684Asn | missense_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.91C>T | p.Arg31Ter | stop_gained | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3190C>T | p.Gln1064Ter | stop_gained | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.3718C>T | p.Arg1240Ter | stop_gained | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.878G>C | p.Arg293Pro | missense_variant | Unknown | - | Unknown | 38563110 | Hye Jin Kim et al. () | |
| c.3748C>T | p.Gln1250Ter | stop_gained | De novo | - | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.3494C>T | p.Ser1165Leu | missense_variant | Unknown | - | - | 27159028 | Fieremans N , et al. (2016) | |
| c.190-2A>G | - | splice_site_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.388-2A>T | - | splice_site_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.828del | p.Lys277ArgfsTer70 | frameshift_variant | De novo | - | - | 34800434 | Chen S et al. (2021) | |
| c.878del | p.Arg293ProfsTer54 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.333del | p.Lys114SerfsTer20 | frameshift_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| c.1030G>A | p.Gly344Ser | missense_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.1352T>C | p.Leu451Pro | missense_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.1513T>C | p.Tyr505His | missense_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.1081C>T | p.Gln361Ter | stop_gained | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2899C>T | p.Arg967Ter | stop_gained | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2956G>T | p.Glu986Ter | stop_gained | De novo | - | Simplex | 37915395 | Giulia Rosti et al. (2023) | |
| c.403C>T | p.Arg135Ter | stop_gained | De novo | - | Simplex | 27334371 | Halvardson J , et al. (2016) | |
| c.1914-1G>A | - | splice_site_variant | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
| c.830dup | p.Lys278GlufsTer6 | frameshift_variant | De novo | - | - | 26544041 | Zhang Y , et al. (2015) | |
| c.1366C>T | p.Gln456Ter | stop_gained | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1735C>T | p.Arg579Ter | stop_gained | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2059C>T | p.Arg687Ter | stop_gained | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2857C>T | p.Arg953Ter | stop_gained | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2857C>T | p.Arg953Ter | stop_gained | Unknown | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2295-1G>A | - | splice_site_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.828del | p.Lys277ArgfsTer70 | frameshift_variant | De novo | - | - | 31031587 | Xiong J , et al. (2019) | |
| c.1685C>T | p.Pro562Leu | missense_variant | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.1741C>T | p.Arg581Trp | missense_variant | De novo | - | Simplex | 29381230 | Kimura Y , et al. (2018) | |
| c.698G>A | p.Cys233Tyr | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.387G>A | p.Ser129= | synonymous_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.2722C>T | p.Arg908Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1652T>C | p.Leu551Pro | missense_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.2047A>G | p.Ile683Val | missense_variant | De novo | - | Simplex | 32277047 | Chevarin M et al. (2020) | |
| c.140G>A | p.Arg47Gln | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.3344T>C | p.Ile1115Thr | missense_variant | Unknown | - | Unknown | 19196676 | Hamdan FF , et al. (2009) | |
| c.3055C>T | p.Arg1019Cys | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.1084T>C | p.Trp362Arg | missense_variant | De novo | - | Simplex | 23161826 | Berryer MH , et al. (2012) | |
| c.1685C>T | p.Pro562Leu | missense_variant | De novo | - | Simplex | 23161826 | Berryer MH , et al. (2012) | |
| c.425A>T | p.Lys142Ile | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.600G>C | p.Leu200Phe | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.3134C>G | p.Ala1045Gly | missense_variant | Unknown | Not tested | - | 24690944 | Brett M , et al. (2014) | |
| c.3158del | p.Pro1053HisfsTer10 | frameshift_variant | De novo | - | - | 29286531 | Tumien B , et al. (2017) | |
| c.3826dup | p.Asp1276GlyfsTer7 | frameshift_variant | De novo | - | - | 30091983 | Gieldon L , et al. (2018) | |
| c.2444G>A | p.Arg815His | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.603T>G | p.Asp201Glu | missense_variant | Unknown | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.844T>C | p.Cys282Arg | missense_variant | Unknown | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1677-2_1685del | - | splice_site_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.403C>T | p.Arg135Ter | stop_gained | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.793A>T | p.Lys265Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1219del | p.Gln407ArgfsTer3 | frameshift_variant | De novo | - | Simplex | 37645600 | Ko YJ et al. (2023) | |
| c.2177_2180del | p.Arg726ThrfsTer33 | frameshift_variant | De novo | - | - | 32469098 | Tang S et al. (2020) | |
| c.2562_2578del | p.Leu855PhefsTer77 | frameshift_variant | De novo | - | - | 32469098 | Tang S et al. (2020) | |
| c.1030G>A | p.Gly344Ser | missense_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1250A>G | p.Tyr417Cys | missense_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1797C>G | p.Cys599Trp | missense_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1889T>A | p.Ile630Asn | missense_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2533G>T | p.Asp845Tyr | missense_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.387G>A | p.Ser129= | splice_site_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.419C>T | p.Ser140Phe | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.387G>A | p.Ser129= | synonymous_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1735C>T | p.Arg579Ter | stop_gained | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1861C>T | p.Arg621Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2059C>T | p.Arg687Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2091G>A | p.Trp697Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2764C>T | p.Arg922Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2899C>T | p.Arg967Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.3345_3353dup | p.Ser1121_Gly1123dup | inframe_insertion | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.333del | p.Lys114SerfsTer20 | frameshift_variant | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.348C>A | p.Tyr116Ter | stop_gained | De novo | - | Extended multiplex | 26989088 | Mignot C , et al. (2016) | |
| c.2974del | p.Val992SerfsTer85 | frameshift_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.743G>A | p.Arg248Gln | missense_variant | Unknown | - | - | 37943464 | Karthika Ajit Valaparambil et al. () | |
| c.3557C>A | p.Ser1186Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.3706C>T | p.Gln1236Ter | stop_gained | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.3718C>T | p.Arg1240Ter | stop_gained | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1178del | p.Gly393AlafsTer10 | frameshift_variant | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.1674del | p.Cys559AlafsTer7 | frameshift_variant | De novo | - | Simplex | 27525107 | Yuen RK et al. (2016) | |
| c.1219del | p.Gln407ArgfsTer3 | frameshift_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.2014del | p.Thr672ArgfsTer2 | frameshift_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| - | - | copy_number_loss | De novo | - | Multiplex (monozygotic twins) | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3657_3658del | p.Tyr1219Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.917_925del | p.Val306_Trp308del | inframe_deletion | De novo | - | Simplex | 36583017 | Wang Y et al. (2022) | |
| c.828dup | p.Lys277GlnfsTer7 | frameshift_variant | Unknown | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.3959C>A | p.Pro1320His | missense_variant | Unknown | - | Multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2630dup | p.Thr878AspfsTer60 | frameshift_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
| c.333del | p.Lys114SerfsTer20 | frameshift_variant | De novo | - | Simplex | 37928246 | Boxuan Li et al. (2023) | |
| c.431_434del | p.Thr144SerfsTer29 | frameshift_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.333del | p.Lys114SerfsTer20 | frameshift_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.509G>A | p.Arg170Gln | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.737T>C | p.Leu246Pro | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.797T>C | p.Leu266Pro | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.844T>C | p.Cys282Arg | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.857T>C | p.Leu286Pro | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.881C>A | p.Thr294Asn | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.531_532del | p.Phe177LeufsTer7 | frameshift_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.1057del | p.Leu353TrpfsTer13 | frameshift_variant | Unknown | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.2933del | p.Pro978HisfsTer99 | frameshift_variant | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.332del | p.Pro111GlnfsTer23 | frameshift_variant | De novo | - | Simplex | 25418537 | O'Roak BJ , et al. (2014) | |
| c.3740_3746del | p.Ile1247SerfsTer2 | frameshift_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
| c.2212_2213del | p.Ser738Ter | frameshift_variant | De novo | - | Simplex | 23161826 | Berryer MH , et al. (2012) | |
| c.1466_1469del | p.Leu489ProfsTer5 | frameshift_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| c.490C>T | p.Arg164Ter | stop_gained | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.427C>T | p.Arg143Ter | stop_gained | De novo | - | Multi-generational | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2396del | p.Leu799ArgfsTer23 | frameshift_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.1221_1224del | p.Thr408Ter | stop_gained | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1717C>T | p.Arg573Trp | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1726T>C | p.Cys576Arg | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.3406dup | p.Gln1136ProfsTer17 | frameshift_variant | Unknown | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.2396del | p.Leu799ArgfsTer23 | frameshift_variant | De novo | - | Simplex | 19196676 | Hamdan FF , et al. (2009) | |
| c.2396del | p.Leu799ArgfsTer23 | frameshift_variant | De novo | - | Simplex | 21376300 | Hamdan FF , et al. (2011) | |
| c.1783del | p.Leu595CysfsTer55 | frameshift_variant | De novo | - | Simplex | 25418537 | O'Roak BJ , et al. (2014) | |
| c.1515C>G | p.Tyr505Ter | stop_gained | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1970G>A | p.Trp657Ter | stop_gained | Unknown | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2059C>T | p.Arg687Ter | stop_gained | De novo | - | Multi-generational | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2874del | p.Asp960ThrfsTer103 | frameshift_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.3583G>A | p.Val1195Met | missense_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2635del | p.Gln879ArgfsTer184 | frameshift_variant | De novo | - | Simplex | 21237447 | Hamdan FF , et al. (2011) | |
| c.2184del | p.Asn729ThrfsTer31 | frameshift_variant | De novo | - | Simplex | 23161826 | Berryer MH , et al. (2012) | |
| c.310C>T | p.Arg104Cys | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.640del | p.Leu214TrpfsTer9 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.828dup | p.Lys277GlnfsTer7 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3505G>T | p.Glu1169Ter | stop_gained | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3657T>G | p.Tyr1219Ter | stop_gained | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3718C>T | p.Arg1240Ter | stop_gained | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.455_459del | p.Arg152GlnfsTer14 | frameshift_variant | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.1465C>T | p.Leu489Phe | missense_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2627G>C | p.Arg876Pro | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1781del | p.Phe594SerfsTer56 | frameshift_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.333del | p.Lys114SerfsTer20 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.690dup | p.Phe231LeufsTer14 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1393del | p.Leu465PhefsTer9 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3545del | p.Glu1182GlyfsTer14 | frameshift_variant | Unknown | Not maternal | - | 27824329 | Wang T , et al. (2016) | |
| c.1670_1671insA | p.His558ProfsTer60 | frameshift_variant | De novo | - | Simplex | 27525107 | Yuen RK et al. (2016) | |
| c.1253_1254del | p.Lys418ArgfsTer54 | frameshift_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
| c.322_326del | p.Lys108CysfsTer42 | frameshift_variant | De novo | - | Simplex | 21237447 | Hamdan FF , et al. (2011) | |
| c.3445C>T | p.Pro1149Ser | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.121C>T | p.Arg41Cys | missense_variant | Unknown | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.2214_2217del | p.Glu739GlyfsTer20 | frameshift_variant | De novo | - | Simplex | 26989088 | Mignot C , et al. (2016) | |
| c.968T>C | p.Leu323Pro | missense_variant | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1154_1161del | p.Ser385TrpfsTer31 | frameshift_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.1167_1168del | p.Gly391GlnfsTer27 | frameshift_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.2520_2536del | p.Leu841PhefsTer77 | frameshift_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.1821_1822del | p.Phe608TrpfsTer9 | frameshift_variant | De novo | - | Simplex | 24267886 | Willsey AJ , et al. (2013) | |
| c.877C>T | p.Arg293Cys | missense_variant | Unknown | Not maternal | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.254_255del | p.Thr85SerfsTer14 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1210G>C | p.Ala404Pro | missense_variant | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3233_3236del | p.Val1078AlafsTer51 | frameshift_variant | Unknown | - | - | 31395010 | Jimenez-Gomez A , et al. (2019) | |
| c.3432_3433insCCAC | p.Asn1145ProfsTer9 | frameshift_variant | De novo | - | Simplex | 38563110 | Hye Jin Kim et al. () | |
| c.1043_1044del | p.Val348AlafsTer70 | frameshift_variant | De novo | - | Simplex | 21076407 | Vissers LE , et al. (2010) | |
| c.2747_2751delinsGTG | p.Val916GlyfsTer21 | frameshift_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.424_427del | p.Lys142GlufsTer31 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.283dup | p.His95ProfsTer5 | frameshift_variant | Familial | Paternal | Simplex | 23161826 | Berryer MH , et al. (2012) | |
| c.2747_2750delinsGTG | p.Val916GlyfsTer161 | frameshift_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
| c.3682_3685del | p.Glu1228LysfsTer6 | frameshift_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.435_447dup | p.Leu150ValfsTer6 | frameshift_variant | De novo | - | Multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1393del | p.Leu465PhefsTer9 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2270del | p.Gly757AlafsTer3 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2177_2180del | p.Arg726ThrfsTer33 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1163del | p.Gly388AlafsTer15 | frameshift_variant | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1722del | p.Arg575AlafsTer75 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1783del | p.Leu595CysfsTer55 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2396del | p.Leu799ArgfsTer23 | frameshift_variant | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2145_2146dup | p.Arg716ProfsTer11 | frameshift_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1167_1168del | p.Gly391GlnfsTer27 | frameshift_variant | De novo | - | Simplex | 34580403 | Pode-Shakked B et al. (2021) | |
| c.2854del | p.His952ThrfsTer111 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.3484del | p.Glu1162LysfsTer28 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2722C>T | p.Gln908Ter | stop_gained | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.2740C>T | p.Gln914Ter | stop_gained | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.3466_3467del | p.Ser1156CysfsTer19 | frameshift_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.1167_1168del | p.Gly391GlnfsTer27 | frameshift_variant | Unknown | - | - | 37943464 | Karthika Ajit Valaparambil et al. () | |
| c.1392_1394dup | p.Leu465dup | inframe_insertion | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.980T>C | p.Leu327Pro | missense_variant | De novo | - | Multiplex (monozygotic twins) | 26079862 | Parker MJ , et al. (2015) | |
| c.1388_1393del | p.Asp463_Leu465delinsVal | inframe_deletion | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1463del | p.Thr488SerfsTer7 | frameshift_variant | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1167_1168del | p.Gly391GlnfsTer27 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1167_1168del | p.Gly391GlnfsTer27 | frameshift_variant | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1171_1172del | p.Gly391GlnfsTer27 | frameshift_variant | De novo | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.2097_2098del | p.Leu700AlafsTer39 | frameshift_variant | Unknown | - | - | 38505260 | Juliana Ribeiro-Constante et al. (2024) | |
| c.1726_1728delinsGGCT | p.Cys576GlyfsTer42 | frameshift_variant | De novo | - | Simplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3364dup | p.Gln1122ProfsTer17 | frameshift_variant | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.1167_1168del | p.Gly391GlnfsTer27 | frameshift_variant | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.3235C>T | p.Gln1079Ter | stop_gained | De novo | - | Multi-generational | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.2936_2938delinsCA | p.Phe979SerfsTer98 | frameshift_variant | De novo | - | Extended multiplex | 30541864 | Vlaskamp DRM , et al. (2018) | |
| c.509G>A | p.Arg170Gln | missense_variant | De novo | - | Multi-generational | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.431_434del | p.Thr144SerfsTer29 | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.2690del | p.Val897AlafsTer166 | frameshift_variant | De novo | - | Multiplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.1552_1555del | p.Tyr518AsnfsTer8 | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| ENSG00000197283:ENST00000293748:exon15:c.G2444A:p.R815H,ENSG00000197283:ENST00000449372:exon14:c.G24 | - | missense_variant | De novo | - | - | 33432195 | Rodin RE et al. (2021) | |
| c.2590_2591insTTAGTGTGTTGGTTAGTAGGCCTAGTATGAGGAGCGTTATGGAGTGGAAGTGAAATCACATGGCTACCTGG | p.Ala864ValfsTer18 | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) |
Common Variants
No common variants reported.
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."
4/1/2021
Score remained at 1
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
1/1/2021
Score remained at 1
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
7/1/2020
Score remained at 1
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
4/1/2020
Score remained at 1
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
Reports Added
[Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability2020] [Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures2020] [Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy2020]1/1/2020
Score remained at 1
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
10/1/2019
Score remained at 1
New Scoring Scheme
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
7/1/2019
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
Reports Added
[Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019] [Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans.2019] [Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and d...2019]4/1/2019
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
Reports Added
[Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with develop...2019] [The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.2019] [Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.2019]1/1/2019
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329. A phenotypic review of 57 individuals with likely pathogenic variants in the SYNGAP1 gene (46 of which had not been previously reported) found that 30 patients had a diagnosis of ASD (53%) (Vlaskamp et al., 2019).
10/1/2018
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329.
7/1/2018
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329.
10/1/2017
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329.
7/1/2017
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as intellectual disability and epilepsy (PMIDs 19196676, 20531469, 21237447, 23020937). Multiple LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23161826, 23708187, 26989088, 27525107, 28554332, 28708303). De novo LoF variants in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886) and in ASD probands from the Autism Sequencing Consortium (PMID 25363760). 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 SYNGAP1 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). Additional de novo LoF variants in SYNGAP1 were identified in an ASD proband from a cohort of 200 Canadian ASD trio families in PMID 27525107 and in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in PMID 27824329.
4/1/2017
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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
[Functional impact of global rare copy number variation in autism spectrum disorders.2010] [De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.2011] [Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [A de novo paradigm for mental retardation.2010] [Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.2011] [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] [Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.2012] [6p21.3 microdeletion involving the SYNGAP1 gene in a patient with intellectual disability, seizures, and severe speech impairment.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.2009] [A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation.2010] [SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family.1998] [A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.1998] [Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking.2005] [Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number.2006] [SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.2006] [Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.2010] [Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity.2013] [SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.2014] [Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruption...2015] [De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.2016] [Identification of Intellectual Disability Genes in Female Patients with A Skewed X Inactivation Pattern.2016] [Mutations in HECW2 are associated with intellectual disability and epilepsy.2016] [Genome-wide characteristics of de novo mutations in autism2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017] [Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental traje...2017]1/1/2017
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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).
10/1/2016
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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).
4/1/2016
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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
[Functional impact of global rare copy number variation in autism spectrum disorders.2010] [De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.2011] [Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.2011] [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] [Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.2012] [6p21.3 microdeletion involving the SYNGAP1 gene in a patient with intellectual disability, seizures, and severe speech impairment.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.2009] [A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation.2010] [SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family.1998] [A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.1998] [Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking.2005] [Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number.2006] [SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.2006] [Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.2010] [Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity.2013] [SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.2014] [Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruption...2015] [De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.2016] [Identification of Intellectual Disability Genes in Female Patients with A Skewed X Inactivation Pattern.2016]1/1/2016
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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
[Functional impact of global rare copy number variation in autism spectrum disorders.2010] [De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.2011] [Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.2011] [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] [Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.2012] [6p21.3 microdeletion involving the SYNGAP1 gene in a patient with intellectual disability, seizures, and severe speech impairment.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.2009] [A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation.2010] [SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family.1998] [A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.1998] [Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking.2005] [Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number.2006] [SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.2006] [Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.2010] [Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity.2013] [SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.2014] [Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruption...2015] [De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015]7/1/2015
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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
[Functional impact of global rare copy number variation in autism spectrum disorders.2010] [De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.2011] [Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.2011] [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] [Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.2012] [6p21.3 microdeletion involving the SYNGAP1 gene in a patient with intellectual disability, seizures, and severe speech impairment.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.2009] [A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation.2010] [SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family.1998] [A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.1998] [Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking.2005] [Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number.2006] [SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.2006] [Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.2010] [Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory.2011] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity.2013] [SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.2014] [Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruption...2015] [De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.2015]4/1/2015
Score remained at 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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 2S to 1S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports. 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 SYNGAP1 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 2S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports.
4/1/2014
Increased from No data to 2S
Description
Several studies have found rare variants in the SYNGAP1 gene to be associated with autism as well as mental retardation and intellectual disability (e.g., PMID 21237447). More recently, an additional eight de novo LoF variants (either predicted in silico or demonstrated experimentally) in SYNGAP1 have been identified in patients with ASD and intellectual disability with or without epilepsy (PMIDs 23020937, 23708187, and 23161826). A de novo LoF variant in SYNGAP1 has also been identified in a simplex ASD case from the Simons Simplex Collection (PMID 24267886). However, a rigorous statistical comparison with controls was not performed in these reports.
Krishnan Probability Score
Score 0.49441785940172
Ranking 3673/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99999844974797
Ranking 327/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.991
Ranking 24/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 3.7250329634198E-7
Ranking 5/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 133
Ranking 4/461 scored genes
[Show Scoring Methodology]