ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3661G>C (p.Glu1221Gln)

dbSNP: rs794726854
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
Center for Bioinformatics, Peking University RCV000180987 SCV000221973 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
Invitae RCV001035456 SCV001198783 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-03-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu1221 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21248271). 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: 190031). This missense change has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy and/or Dravet syndrome (PMID: 26096185; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1221 of the SCN1A protein (p.Glu1221Gln).

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.