ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.5212C>T (p.Arg1738Trp) (rs199473303)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
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 RCV000058751 SCV000090271 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:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762372 SCV000892684 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000824908 SCV000965836 pathogenic Sick sinus syndrome 1, autosomal recessive 2016-01-01 criteria provided, single submitter clinical testing
Invitae RCV000545771 SCV000637173 uncertain significance Brugada syndrome 2017-01-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1739 of the SCN5A protein (p.Arg1739Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs199473303, ExAC 0.02%). This variant has been reported in an individual referred for long QT syndrome genetic testing (PMID: 19716085), and has also been observed in a control individual (PMID: 25904541). ClinVar contains an entry for this variant (Variation ID: 67965). This variant identified in the SCN5A gene is located in the transmembrane spanning DIV-S5/S6 region of the resulting protein (PMID: 25348405). For more information about the location of this variant, please visit www.invitae.com/SCN5A-topology. It is unclear how this variant impacts the function of this protein. 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. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role 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.