ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.5576G>A (p.Arg1859Lys)

dbSNP: rs1559720220
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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 RCV001841896 SCV000907120 uncertain significance Cardiac arrhythmia 2019-05-05 criteria provided, single submitter clinical testing This missense variant replaces arginine with lysine at codon 1860 of the SCN5A protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact 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 nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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 RCV001056733 SCV001221195 uncertain significance Brugada syndrome 2022-02-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1860 of the SCN5A protein (p.Arg1860Lys). This variant is not present in population databases (gnomAD no frequency). 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: 628763). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV002343624 SCV002647333 uncertain significance Cardiovascular phenotype 2021-01-05 criteria provided, single submitter clinical testing The p.R1860K variant (also known as c.5579G>A), located in coding exon 27 of the SCN5A gene, results from a G to A substitution at nucleotide position 5579. The arginine at codon 1860 is replaced by lysine, an amino acid with highly similar properties. This variant has been reported in a long QT syndrome (LQTS) cohort; however, clinical details were limited and additional variants were identified in some cases (Gibbs C et al. J Am Heart Assoc, 2018 08;7:e009706). This amino acid position is highly 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.

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