ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3079C>T (p.Arg1027Trp)

gnomAD frequency: 0.00001  dbSNP: rs1455337011
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005092036 SCV000831053 uncertain significance not provided 2024-04-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1027 of the SCN5A protein (p.Arg1027Trp). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy or sudden infant death syndrome (PMID: 24981977, 29544605). ClinVar contains an entry for this variant (Variation ID: 579030). 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.
Color Diagnostics, LLC DBA Color Health RCV001841872 SCV001347058 uncertain significance Cardiac arrhythmia 2022-12-12 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the linker region between transmembrane domains DII and DIII of the SCN5A protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant 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 affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 24981977) and in an infant affected with sudden death (PMID: 29544605). This variant has been identified in 1/245462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Ambry Genetics RCV002319563 SCV002606813 uncertain significance Cardiovascular phenotype 2020-08-08 criteria provided, single submitter clinical testing The p.R1027W variant (also known as c.3079C>T), located in coding exon 16 of the SCN5A gene, results from a C to T substitution at nucleotide position 3079. The arginine at codon 1027 is replaced by tryptophan, an amino acid with dissimilar properties, and is located in the DII/DIII region. This variant has been reported in sudden death cohorts, but clinical details have been limited (Brion M et al. Electrophoresis, 2014 Nov;35:3111-6; Tester DJ et al. J. Am. Coll. Cardiol., 2018 03;71:1217-1227). This amino acid position is not 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.
Fulgent Genetics, Fulgent Genetics RCV002485729 SCV002800938 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2021-11-18 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001841872 SCV004817198 uncertain significance Cardiac arrhythmia 2024-02-22 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the linker region between transmembrane domains DII and DIII of the SCN5A protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant 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 affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 24981977) and in an infant affected with sudden death (PMID: 29544605). This variant has been identified in 1/245462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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