ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.577T>C (p.Trp193Arg)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003873608 SCV004677208 uncertain significance not provided 2023-09-27 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 193 of the SCN5A protein (p.Trp193Arg).
All of Us Research Program, National Institutes of Health RCV004805103 SCV005424004 uncertain significance Cardiac arrhythmia 2024-02-22 criteria provided, single submitter clinical testing This missense variant replaces tryptophan with arginine at codon 193 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual suspected of having Brugada syndrome (PMID: 26743238). This variant has been identified in 1/238184 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.
GeneDx RCV003873608 SCV005889475 uncertain significance not provided 2024-09-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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