ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1642C>T (p.Arg548Cys) (rs550400909)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000551660 SCV000641965 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2019-04-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 548 of the DSG2 protein (p.Arg548Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs550400909, ExAC 0.002%). This variant has not been reported in the literature in individuals with DSG2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Color Health, Inc RCV001186978 SCV001353617 uncertain significance Cardiomyopathy 2020-11-25 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 548 of the DSG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a sudden cardiac arrest survivor (PMID: 30975432). This variant has been identified in 6/279360 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.

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