ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4631A>G (p.Asp1544Gly) (rs1573964628)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000810151 SCV000950341 likely pathogenic Early infantile epileptic encephalopathy 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 1544 of the SCN1A protein (p.Asp1544Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Dravet syndrome (PMID: 21248271). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Asp1544 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 18930999), which suggests that this may be a clinically significant amino acid residue. 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.

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.