ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.713C>T (p.Thr238Ile)

gnomAD frequency: 0.00001  dbSNP: rs767523704
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001182796 SCV001348377 likely benign Cardiomyopathy 2024-08-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001340500 SCV001534314 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2020-06-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 238 of the DSG2 protein (p.Thr238Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs767523704, ExAC 0.006%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine 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.
Ambry Genetics RCV002365863 SCV002665488 likely benign Cardiovascular phenotype 2025-02-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
All of Us Research Program, National Institutes of Health RCV004008325 SCV004819468 likely benign Arrhythmogenic right ventricular cardiomyopathy 2023-08-15 criteria provided, single submitter clinical testing

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