ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.625C>T (p.Arg209Cys)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002366717 SCV002656461 uncertain significance Cardiovascular phenotype 2022-12-12 criteria provided, single submitter clinical testing The p.R209C variant (also known as c.625C>T), located in coding exon 5 of the SCN10A gene, results from a C to T substitution at nucleotide position 625. The arginine at codon 209 is replaced by cysteine, an amino acid with highly dissimilar properties. An alternate amino acid substitution at this position, p.R209H, has been reported in an individual with persistent atrial fibrillation on a known QT-prolonging medication, who had significantly prolonged QTc values (Abou Ziki MD et al. Clin. Genet., 2018 Apr;93:741-751). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003098182 SCV003466041 uncertain significance Brugada syndrome 2022-08-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 209 of the SCN10A protein (p.Arg209Cys). This variant is present in population databases (rs138262927, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
CeGaT Center for Human Genetics Tuebingen RCV003434474 SCV004154216 uncertain significance not provided 2023-10-01 criteria provided, single submitter clinical testing
GeneDx RCV003434474 SCV005079121 uncertain significance not provided 2024-06-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis indicates that this missense variant does not alter protein structure/function

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