ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1272C>G (p.Ile424Met)

dbSNP: rs267599794
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001843274 SCV001352354 likely benign Cardiac arrhythmia 2020-07-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002447012 SCV002683067 uncertain significance Cardiovascular phenotype 2021-03-12 criteria provided, single submitter clinical testing The p.I424M variant (also known as c.1272C>G), located in coding exon 9 of the SCN5A gene, results from a C to G substitution at nucleotide position 1272. The isoleucine at codon 424 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003658106 SCV003011720 uncertain significance not provided 2022-08-09 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. 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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 924597). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is present in population databases (rs267599794, gnomAD 0.05%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 424 of the SCN5A protein (p.Ile424Met).
GeneDx RCV003658106 SCV005078800 uncertain significance not provided 2024-06-10 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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