ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1612C>T (p.Pro538Ser)

gnomAD frequency: 0.00001  dbSNP: rs766053352
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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 RCV001186344 SCV001352737 uncertain significance Cardiomyopathy 2023-01-27 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 538 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 reported for this variant. This variant has not been reported in individuals affected with DSG2-related disorders in the literature. This variant has been identified in 1/249220 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 RCV001876181 SCV002313145 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-07-19 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 924759). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 538 of the DSG2 protein (p.Pro538Ser).
All of Us Research Program, National Institutes of Health RCV004008592 SCV004819564 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-02-24 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces proline with serine at codon 538 of the DSG2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/245876 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.

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