ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1722C>A (p.Asp574Glu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001040152 SCV001203713 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2019-01-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 574 of the DSG2 protein (p.Asp574Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSG2-related conditions. 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.
Color Health, Inc RCV001524519 SCV001734406 uncertain significance Cardiomyopathy 2020-11-11 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 574 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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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