ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3165dup (p.Thr1056fs)

dbSNP: rs2073312554
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177731 SCV001341994 uncertain significance Cardiomyopathy 2019-01-31 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant inserts 1 nucleotide in the last exon 15 of the DSG2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. 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 is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.
Invitae RCV003631180 SCV004521409 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1056Hisfs*11) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 63 amino acid(s) of the DSG2 protein. 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: 919496). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the DSG2 protein in which other variant(s) (p.Gly1083Ser) have been observed in individuals with DSG2-related conditions (PMID: 21636032). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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.

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