Developmental Brain Disorder Gene Database

LoF Variant Gene

Gene
Search

Tier

1

SCN1A

HGNC:10585 (protein-coding gene)

sodium voltage-gated channel alpha subunit 1

Unique Cases:
230
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
November 4, 2024

Gene Summary:

DBD Genes Classification
SCN1A is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage- gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient... (Source: Uniprot)
Previous symbols
SCN1, FEB3
Alias symbols
Nav1.1, GEFSP2, HBSCI, NAC1, SMEI
Chromosomal Location
2q24.3
Genomic Coordinates
GRCh37:chr2:166845670-167005642
GRCh38:chr2:165984641-166149161
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

9.08

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.07

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Strong1

Definitive2

Moderate1

GenCC Classification (GenCC)

Definitive6 Moderate2 Strong5 Supportive6

Publications:

Na JH et. al., Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy., Brain Dev, 2020
Stödberg T et. al., Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study., Epilepsia, 2020
Riva D et. al., Progressive neurocognitive decline in two children with Dravet syndrome, de novo SCN1A truncations and different epileptic phenotypes., Am J Med Genet A, 2009
Møller RS et. al., Parental mosaicism in epilepsies due to alleged de novo variants., Epilepsia, 2019
Lim BC et. al., SCN1A mutational analysis in Korean patients with Dravet syndrome., Seizure, 2011
Le Gal F et. al., A case of SUDEP in a patient with Dravet syndrome with SCN1A mutation., Epilepsia, 2010
Kumakura A et. al., Novel de novo splice-site mutation of SCN1A in a patient with partial epilepsy with febrile seizures plus., Brain Dev, 2009
Gökben S et. al., An inherited nonsense R1645X mutation in neuronal sodium channel alpha1-subunit gene in a Turkish patient with severe myoclonic epilepsy of infancy., Neuropediatrics, 2009
Gitiaux C et. al., Motor neuropathy contributes to crouching in patients with Dravet syndrome., Neurology, 2016
Fujiwara T et. al., Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures., Brain, 2003
de Lange IM et. al., Mosaicism of de novo pathogenic SCN1A variants in epilepsy is a frequent phenomenon that correlates with variable phenotypes., Epilepsia, 2018
Ceulemans B et. al., Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine., Epilepsia, 2016
Barba C et. al., Co-occurring malformations of cortical development and SCN1A gene mutations., Epilepsia, 2014
Ozmen M et. al., Severe myoclonic epilepsy of infancy (Dravet syndrome): Clinical and genetic features of nine Turkish patients., Ann Indian Acad Neurol, 2011
McArdle EJ et. al., Novel SCN1A frameshift mutation with absence of truncated Nav1.1 protein in severe myoclonic epilepsy of infancy., Am J Med Genet A, 2008
Balestrini S et. al., Audit of use of stiripentol in adults with Dravet syndrome., Acta Neurol Scand, 2017
Willemsen MH et. al., Adult Phenotypes in Angelman- and Rett-Like Syndromes., Mol Syndromol, 2012
Kwong AK et. al., Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome., PLoS One, 2012
Do TT et. al., SCN1A Gene Mutation and Adaptive Functioning in 18 Vietnamese Children with Dravet Syndrome., J Clin Neurol, 2017
Trump N et. al., Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis., J Med Genet, 2016
Helbig KL et. al., Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy., Genet Med, 2016
Kodera H et. al., Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy., Epilepsia, 2013
D'Gama AM et. al., Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms., Neuron, 2015
van Egmond ME et. al., Myoclonus in childhood-onset neurogenetic disorders: The importance of early identification and treatment., Eur J Paediatr Neurol, 2015
Sharkia R et. al., Parental mosaicism in another case of Dravet syndrome caused by a novel SCN1A deletion: a case report., J Med Case Rep, 2016
Xiong Z et. al., Dravet syndrome with autism inherited from a paternal mosaic heterozygous mutation on SCN1A., J Neurol Sci, 2016
Usluer S et. al., SCN1A gene sequencing in 46 Turkish epilepsy patients disclosed 12 novel mutations., Seizure, 2016
Lemke JR et. al., Targeted next generation sequencing as a diagnostic tool in epileptic disorders., Epilepsia, 2012
Jang SS et. al., Diagnostic Yield of Epilepsy Panel Testing in Patients With Seizure Onset Within the First Year of Life., Front Neurol, 2019
Peng J et. al., Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy., CNS Neurosci Ther, 2019
Yang L et. al., Clinical and genetic spectrum of a large cohort of children with epilepsy in China., Genet Med, 2019
Mahdieh N et. al., Pathogenic significance of SCN1A splicing variants causing Dravet syndrome: Improving diagnosis with targeted sequencing for variants by in silico analysis., Clin Neurol Neurosurg, 2018
Jiang T et. al., Clinical and molecular analysis of epilepsy-related genes in patients with Dravet syndrome., Medicine (Baltimore), 2018
Allen AS et. al., De novo mutations in epileptic encephalopathies., Nature, 2013
Passamonti C et. al., A novel inherited SCN1A mutation associated with different neuropsychological phenotypes: is there a common core deficit?, Epilepsy Behav, 2015
Hesse AN et. al., Retrospective genotype-phenotype analysis in a 305 patient cohort referred for testing of a targeted epilepsy panel., Epilepsy Res, 2018
Fry AE et. al., Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy., BMC Med Genet, 2016
Carvill GL et. al., Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1., Nat Genet, 2013
Coe BP et. al., Refining analyses of copy number variation identifies specific genes associated with developmental delay., Nat Genet, 2014
Jiang P et. al., Dravet syndrome with favourable cognitive and behavioral development due to a novel SCN1A frameshift mutation., Clin Neurol Neurosurg, 2016
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Nouri N et. al., Clinical and genetic profile of children with unexplained intellectual disability/developmental delay and epilepsy., Epilepsy Res, 2021
Jiang T et. al., Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy., Front Mol Neurosci, 2021
Nejabat M et. al., Genetic Testing in Various Neurodevelopmental Disorders Which Manifest as Cerebral Palsy: A Case Study From Iran., Front Pediatr, 2021
Al Zahrani H et. al., Genomics in Cerebral Palsy phenotype across the lifespan: Comparison of diagnostic yield between children and adult population., Mol Genet Metab, 2021
May HJ et. al., Genetic testing in individuals with cerebral palsy., Dev Med Child Neurol, 2021
Lee HF et. al., Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders., Dev Med Child Neurol, 2021
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
Lee J et. al., Genetic Diagnosis of Dravet Syndrome Using Next Generation Sequencing-Based Epilepsy Gene Panel Testing., Ann Clin Lab Sci, 2020
Sun D et. al., Detection of Disease-Causing SNVs/Indels and CNVs in Single Test Based on Whole Exome Sequencing: A Retrospective Case Study in Epileptic Encephalopathies., Front Pediatr, 2021
Zhao X et. al., Genetic analysis and identification of novel variations in Chinese patients with pediatric epilepsy by whole-exome sequencing., Neurol Sci, 2022
Brea-Fernández AJ et. al., Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability., Eur J Hum Genet, 2022
Mulley JC et. al., A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A., Neurology, 2006
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NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
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