ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1693A>G (p.Ile565Val)

gnomAD frequency: 0.00001  dbSNP: rs780712159
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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 RCV001183264 SCV001348948 uncertain significance Cardiomyopathy 2023-06-07 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 565 of the DSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy and sudden cardiac death (PMID: 27000522). This variant has been identified in 3/250746 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Invitae RCV001223657 SCV001395814 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2022-05-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 565 of the DSC2 protein (p.Ile565Val). This variant is present in population databases (rs780712159, gnomAD 0.002%). This missense change has been observed in individual(s) with sudden death and arrhythmogenic right ventricular cardiomyopathy (PMID: 27000522). ClinVar contains an entry for this variant (Variation ID: 922920). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV001223657 SCV002800933 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2021-10-30 criteria provided, single submitter clinical testing

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