ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.589G>T (p.Asp197Tyr)

dbSNP: rs1553605667
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV000853441 SCV000996352 uncertain significance Primary dilated cardiomyopathy 2017-09-12 criteria provided, single submitter research The SCN5A Asp197Tyr variant has been previously identified in 2 individuals from a family with a mixed cardiac phenotype (Genedx, personal comm.). The variant is absent from the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). Computational SIFT, PolyPhen2 and MutationTaster suggest that the variant is deleterious. We identified this variant in patient with mild left ventricular dilation and conduction system disease. The variant was also found to segregate to the probands sibling who has DCM and conduction system disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV003658427 SCV003310639 uncertain significance not provided 2022-09-10 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. This variant disrupts the p.Asp197 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31477192; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 201435). This missense change has been observed in individual(s) with SCN5A-related conditions (PMID: 33221895). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 197 of the SCN5A protein (p.Asp197Tyr).

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