ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2079A>C (p.Glu693Asp) (rs375595872)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691323 SCV000819099 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2018-01-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 693 of the DSG2 protein (p.Glu693Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs375595872, ExAC 0.003%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 RCV001186672 SCV001353212 uncertain significance Cardiomyopathy 2020-07-15 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with aspartic acid at codon 693 of the DSG2 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 performed 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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