ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1750C>T (p.Gln584Ter)

gnomAD frequency: 0.00001  dbSNP: rs794728086
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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 RCV000227785 SCV000287231 pathogenic Arrhythmogenic right ventricular dysplasia 10 2024-04-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln584*) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 17105751, 31386562). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 199810). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
All of Us Research Program, National Institutes of Health RCV003996618 SCV004841985 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-07-20 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 12 of the DSG2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 31386562). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion for a pathogenic role, clinical significance of loss-of-function DSG2 variants in autosomal dominant arrhythmogenic cardiomyopathy is not yet clearly established. 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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