ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.6025A>G (p.Arg2009Gly)

gnomAD frequency: 0.00003  dbSNP: rs753744525
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001842782 SCV001344168 uncertain significance Cardiac arrhythmia 2019-11-26 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 2010 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 6/190746 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003656666 SCV001503294 uncertain significance not provided 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2010 of the SCN5A protein (p.Arg2010Gly). This variant is present in population databases (rs753744525, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 920643). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
All of Us Research Program, National Institutes of Health RCV001842782 SCV004827489 uncertain significance Cardiac arrhythmia 2023-05-31 criteria provided, single submitter clinical testing

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