ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.643A>G (p.Asn215Asp)

dbSNP: rs879255695
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001854934 SCV002132008 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-11-08 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 215 of the SCN8A protein (p.Asn215Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN8A-related conditions (PMID: 25568300, 28135719; Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as g.52082570A>G. ClinVar contains an entry for this variant (Variation ID: 253277). 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 SCN8A protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SCN8A function (PMID: 32916281). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000239741 SCV000298184 not provided Developmental and epileptic encephalopathy, 13 no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.