ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.242A>G (p.Asp81Gly)

dbSNP: rs1684663181
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology RCV001030755 SCV001189952 uncertain significance Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2020-03-04 criteria provided, single submitter clinical testing The c.242A>G variant is not present in publicly available databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP. The variant is not present in our in-house exome database. The variant is also not present in our in-house exome database. The variant was not reported earlier to OMIM, ClinVar or HGMD databases. In-silico pathogenicity prediction programs like SIFT, PolyPhen2, MutationTaster2, CADD etc. predicted this variant as likely deleterious, however there are no existing functional studies to prove this. Due to lack of enough evidence the variant has been classified as uncertain significance.
Invitae RCV001379829 SCV001577701 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2021-12-02 criteria provided, single submitter clinical testing 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 variant disrupts the p.Asp81 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26169758, 27236449, 29745119). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 830315). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 81 of the SCN1A protein (p.Asp81Gly).

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