ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1460T>G (p.Ile487Ser)

gnomAD frequency: 0.00001  dbSNP: rs776525113
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001805336 SCV002052493 uncertain significance Cardiomyopathy 2021-03-08 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with serine at codon 487 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 been identified in 3/249344 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001885275 SCV002248266 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2021-11-20 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs776525113, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 487 of the DSG2 protein (p.Ile487Ser).
All of Us Research Program, National Institutes of Health RCV004009123 SCV004819542 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with serine at codon 487 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 been identified in 3/249344 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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