ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3144_3147del (p.Arg1049fs) (rs758822081)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482922 SCV000569072 uncertain significance not provided 2016-10-10 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DSG2 gene. The c.3144_3147delAAGA variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. The c.3144_3147delAAGA variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant causes a shift in reading frame starting at codon Arginine 1049, changing it to a Phenylalanine, and creating a premature stop codon at position 2 of the new reading frame, denoted p.Arg1049PhefsX2. The c.3144_3147delAAGA variant is expected to result in an abnormal, truncated protein product as it causes loss of the last 70 amino acid residues of the protein and replacement with one incorrect amino acid. While other frameshift variants in the DSG2 gene have been reported in the Human Gene Mutation Database in association with ARVD/C, none have been reported downstream of this variant (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Invitae RCV001212540 SCV001384127 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-07-24 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the DSG2 gene (p.Arg1049Phefs*2). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 70 amino acids of the DSG2 protein. This variant is present in population databases (rs758822081, ExAC 0.009%). This variant has not been reported in the literature in individuals with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 420292). Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.

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.