ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.663T>A (p.Tyr221Ter) (rs145476705)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000149890 SCV000196738 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2014-06-01 criteria provided, single submitter research
GeneDx RCV000181141 SCV000233418 pathogenic not provided 2014-04-03 criteria provided, single submitter clinical testing p.Tyr221Stop (TAT>TAA): c.663 T>A in exon 6 of the DSC2 gene (NM_024422.3). Although rare, mutations in the DSC2 gene have been reported in association with ARVC (McNally E et al., 2009).The Y221X mutation in the DSC2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Dorschner et al. (2013) reported Y221X in one individual out of 1000 individuals randomly selected from the NHLBI Exome Sequencing Project cohort and listed Y221X as a disruptive variant not listed as disease causing". Y221X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other truncating mutations in the DSC2 gene have been reported in association with ARVC. In summary, Y221X in the DSC2 gene is interpreted as a disease-causing mutation. The variant is found in CARDIOMYOPATHY panel(s)."
Invitae RCV000458517 SCV000551451 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 11 2019-10-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr221*) in the DSC2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs145476705, ExAC 0.01%). This variant has not been reported in the literature in individuals with DSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 162504). Loss-of-function variants in DSC2 are known to be pathogenic (PMID: 18957847, 23863954, 23911551). For these reasons, this variant has been classified as Pathogenic.

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