ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1938T>G (p.Tyr646Ter)

gnomAD frequency: 0.00002  dbSNP: rs397517395
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000039415 SCV000063099 uncertain significance not specified 2018-02-02 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Color Diagnostics, LLC DBA Color Health RCV001183803 SCV001349630 uncertain significance Cardiomyopathy 2019-09-23 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 13 of the DSC2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in two individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 27532257). This variant has been identified in 2/282132 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical significance of loss-of-function variants in the DSC2 gene is not clearly established. The 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.
GeneDx RCV002468994 SCV002765238 likely pathogenic not provided 2022-12-10 criteria provided, single submitter clinical testing Reported in two patients referred for arrhythmogenic right ventricular cardiomyopathy (ARVC) genetic testing (Walsh et al., 2017); however, detailed clinical information was not provided; Not observed at a significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27532257, 31402444)
All of Us Research Program, National Institutes of Health RCV004806039 SCV005427446 uncertain significance Familial isolated arrhythmogenic right ventricular dysplasia 2024-08-06 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 13 of the DSC2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in two individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 27532257). This variant has been identified in 2/282132 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical significance of loss-of-function variants in the DSC2 gene is not clearly established. The 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.

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