ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1773_1774del (p.Cys591_Glu592delinsTer)

dbSNP: rs397516703
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037271 SCV000060928 pathogenic Arrhythmogenic right ventricular cardiomyopathy 2018-04-23 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000181243 SCV000233522 pathogenic not provided 2021-07-12 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; A different nucleotide change (c.1773 T>A) leading to the same nonsense variant has been reported in HGMD (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 27535533, 31402444, 25157032, 21606390, 17105751, 19279339, 19095136)
AiLife Diagnostics, AiLife Diagnostics RCV000181243 SCV002501801 pathogenic not provided 2022-01-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003517132 SCV004297822 pathogenic Arrhythmogenic right ventricular dysplasia 10 2023-07-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys591*) 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 present in population databases (rs774105846, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of DSG2-related conditions (PMID: 17105751). ClinVar contains an entry for this variant (Variation ID: 44286). For these reasons, this variant has been classified as Pathogenic.
All of Us Research Program, National Institutes of Health RCV000037271 SCV004836346 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-12-18 criteria provided, single submitter clinical testing This variant deletes 2 nucleotides in exon 12 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 studies have not been reported for this variant. This variant has been reported in at least three unrelated individuals affected with arrhythmogenic cardiomyopathy (PMID: 17105751, 19095136, 25157032) and has been shown to segregate with disease in two families (PMID: 17105751, 25157032). The p.Cys591* variant has been identified in a 45 year old patient with ARVC (PMID: 19279339). This variant has been identified in 1/249168 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may be associated with disease, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.