ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2507T>C (p.Leu836Pro)

dbSNP: rs1425278506
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001319076 SCV001509803 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 836 of the DSG2 protein (p.Leu836Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected 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. 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 Diagnostics, LLC DBA Color Health RCV001525649 SCV001735823 uncertain significance Cardiomyopathy 2020-08-17 criteria provided, single submitter clinical testing This missense variant replaces leucine with proline at codon 836 of the DSG2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 1/249112 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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