ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.986G>C (p.Gly329Ala)

dbSNP: rs779184118
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001334845 SCV001527813 likely pathogenic Severe myoclonic epilepsy in infancy 2018-10-19 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 28084635]
Labcorp Genetics (formerly Invitae), Labcorp RCV002546700 SCV003458802 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 329 of the SCN1A protein (p.Gly329Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with genetic epilepsy with febrile seizures plus (PMID: 28084635). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1032678). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function with a positive predictive value of 95%. This variant disrupts the p.Gly329 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32538476; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004789531 SCV005401426 likely pathogenic not provided 2024-05-08 criteria provided, single submitter clinical testing This substitution is predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the first homologous domain; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28084635)

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