ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5173G>A (p.Gly1725Ser)

dbSNP: rs1689280236
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV001289475 SCV001477309 likely pathogenic Severe myoclonic epilepsy in infancy 2020-11-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003753171 SCV004412075 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-11-23 criteria provided, single submitter clinical testing This variant disrupts the p.Gly1725 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29142202; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1725 of the SCN1A protein (p.Gly1725Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 995420). 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.

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