ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.875G>T (p.Arg292Leu) (rs185821167)

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 RCV000181210 SCV000233488 likely pathogenic not provided 2012-10-12 criteria provided, single submitter clinical testing p.Arg292Leu (CGC>CTC):c.875 G>T in exon 8 of the DSG2 gene (NM_001943.3). The Arg292Leu variant in the DSG2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg292Leu results in a non-conservative amino acid substitution of a positively charged Arginine with a non-polar Leucine at a position that is conserved across species. A mutation at the same codon (Arg292Cys) and mutations in nearby residues (Lys294Glu, Asp297Gly) have been reported in association with ARVC, further supporting the functional importance of this codon and this region of the protein. In silico analysis predicts Arg292Leu is probably damaging to the protein structure/function. Furthermore, the NHLBI ESP Exome Variant Server reports Arg292Leu was not observed in approximately 6000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, Arg292Leu is a good candidate for a disease-causing mutation.The variant is found in ARVC panel(s).
Invitae RCV000465847 SCV000551020 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2016-04-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 292 of the DSG2 protein (p.Arg292Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DSG2-related disease. ClinVar contains an entry for this variant (Variation ID: 199802). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. 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.