ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.677C>T (p.Ala226Val) (rs199473561)

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
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058837 SCV000090357 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:11901046;PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Invitae RCV000058837 SCV000637202 uncertain significance Brugada syndrome 2017-12-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 226 of the SCN5A protein (p.Ala226Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs199473561, ExAC 0.2%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with Brugada syndrome (PMID: 11901046, 14967853, 20129283, 25829473). In one of these cases it was found in the compound heterozygous state with a pathogenic SCN5A variant (PMID: 25829473). ClinVar contains an entry for this variant (Variation ID: 68034). Experimental studies have shown that this missense change reduces the channel sodium current (PMID: 25829473). In summary, this variant has been reported in affected individuals and there is some functional evidence showing that it causes a deleterious effect on protein function. However, it is present at a relatively high frequency in the general population. For these reasons it has been classified as a variant of Uncertain significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000454727 SCV000540294 uncertain significance not specified 2016-12-16 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has been reported in an individual with Brugada syndrome who was compound het for this and an Arg1629X variant in SCN5A. Electrophysiological experiments showed that the variant had little effect on current density alone (Tan 2015). It was identified in 3 additional patients with Brugada syndrome. This variant is present in ClinVar with no classification. It has a Max MAF of 0.18% in ExAC (9 alleles) and 0.13% in gnomAD (25 alleles). This variant is predicted to be pathogenic by prediction tools.

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.