ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1555G>T (p.Asp519Tyr) (rs778119035)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181221 SCV000233500 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000803625 SCV000943505 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-02-14 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 519 of the DSG2 protein (p.Asp519Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs778119035, ExAC 0.01%). This variant has not been reported in the literature in individuals with DSG2-related disease. ClinVar contains an entry for this variant (Variation ID: 199809). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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