Submissions for variant NM_001165963.4(SCN1A):c.2791C>A (p.Arg931Ser)

dbSNP: rs121918788

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital	RCV001530193	SCV001739485	likely pathogenic	Severe myoclonic epilepsy in infancy	2020-02-28	criteria provided, single submitter	clinical testing
Invitae	RCV002568884	SCV003310613	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2022-04-24	criteria provided, single submitter	clinical testing	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. This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 931 of the SCN1A protein (p.Arg931Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epileptic encephalopathy (PMID: 34539730). In at least one individual the variant was observed to be de novo. This variant is also known as c.2758C>A (p.Arg920Ser). ClinVar contains an entry for this variant (Variation ID: 1175195). This variant disrupts the p.Arg931 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12083760, 18076640). 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.
Department of Developmental Neurology, Medical University of Gdańsk	RCV001530193	SCV004100902	not provided	Severe myoclonic epilepsy in infancy		no assertion provided	phenotyping only