ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.5384A>G (p.Tyr1795Cys) (rs137854614)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698334 SCV000826994 pathogenic Brugada syndrome 2018-03-20 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1795 of the SCN5A protein (p.Tyr1795Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with long QT syndrome in two families (PMID: 11410597, 18929331) and has been reported in an individual with this condition (PMID: 22129298). ClinVar contains an entry for this variant (Variation ID: 9375). Experimental studies have shown that this missense change disrupts SCN5A channel function causing a sustained inward sodium channel current and slowing the onset of inactivation with a prolongation of the action potential (PMID: 11410597, 14990510, 16254012). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000009969 SCV000030190 pathogenic Long QT syndrome 3 2001-08-17 no assertion criteria provided literature only
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058778 SCV000090298 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:11410597;PMID:15840476;PMID:19716085;PMID:19841300;PMID:18929331). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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.