ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.4293G>T (p.Arg1431Ser)

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 RCV000817062 SCV000957600 uncertain significance Brugada syndrome 2018-07-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 1432 of the SCN5A protein (p.Arg1432Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Brugada syndrome (Invitae). 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. A different variant (c.4296G>C) giving rise to the same protein effect observed here (p.Arg1432Ser) has been reported in an individual affected with Brugada syndrome (PMID: 28341781) and in an individual affected with long QT syndrome or referred for long QT syndrome clinical genetic testing (PMID: 25904541), indicating that this residue may be critical for protein function. The observation of one or more missense substitutions at this codon (p.Arg4132Ser and p.Arg4132Gly) in affected individuals suggests that this may be a clinically significant residue (PMID: 28341781, 10727653, 25904541). 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.

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.