ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1654G>C (p.Gly552Arg)

dbSNP: rs3918389
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001840969 SCV001353352 uncertain significance Cardiac arrhythmia 2019-01-08 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the cytoplasmic linker region between transmembrane domains DI and DII of the SCN5A protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual referred for Brugada syndrome genetic testing (PMID: 20129283) and in an individual affected with Brugada syndrome (Seo et al., 2006 ASHG abstract). This variant has also been identified in 5/246142 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.
Invitae RCV003727946 SCV004548609 uncertain significance not provided 2023-02-02 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects SCN5A function (PMID: 24573164). 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. ClinVar contains an entry for this variant (Variation ID: 925037). This missense change has been observed in individual(s) with SCN5A-related conditions (PMID: 20129283, 25904541). This variant is present in population databases (rs3918389, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 552 of the SCN5A protein (p.Gly552Arg).

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.