ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2343_2344insAAGA (p.Ser782fs)

dbSNP: rs1252006527
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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 RCV001180681 SCV001345676 uncertain significance Cardiomyopathy 2023-05-10 criteria provided, single submitter clinical testing This variant inserts 4 nucleotides in exon 15 of the DSG2 gene, creating a frameshift and premature translation stop signal in the last exon. The mutant transcript is expected to escape nonsense-mediated decay and be expressed as a protein product containing altered C-terminal sequence. To our knowledge, this variant has not been reported in individuals affected with DSG2-related disorders in the literature. This variant has not been identified 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.
Invitae RCV001875995 SCV002186204 pathogenic Arrhythmogenic right ventricular dysplasia 10 2022-03-08 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with DSG2-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DSG2 protein in which other variant(s) (p.Glu1020Alafs*18) have been determined to be pathogenic (PMID: 20864495, 21397041, 23381804). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 921330). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser782Lysfs*5) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 337 amino acid(s) of the DSG2 protein.

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