ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.1700T>A (p.Leu567Gln) (rs199473124)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619630 SCV000738223 uncertain significance Cardiovascular phenotype 2017-11-27 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000058442 SCV000813706 uncertain significance Brugada syndrome 2019-09-18 criteria provided, single submitter clinical testing This sequence change replaces leucine with glutamine at codon 567 of the SCN5A protein (p.Leu567Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is present in population databases (rs199473124, ExAC 0.002%). This variant has been reported to segregate with disease in a family affected with Brugada syndrome (PMID: 10711933). Additionally, it has been reported in an individual affected with Brugada syndrome (PMID: 11076825) and an individual who suffered a sudden unexplained death (PMID: 29915097). ClinVar contains an entry for this variant (Variation ID: 67678). Experimental studies have shown that this missense change causes a decrease in current density and a negative shift in the voltage dependence of inactivation in vitro and in rat and human cardiomyocytes (PMID: 24573164, 11123251). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000776285 SCV000911572 uncertain significance Arrhythmia 2019-10-16 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845516 SCV000987619 likely pathogenic Long QT syndrome criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058442 SCV000089962 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:10711933;PMID:11901046;PMID:11076825;PMID:11123251). 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.