ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.806T>C (p.Ile269Thr)

gnomAD frequency: 0.00003  dbSNP: rs727502986
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 RCV000150536 SCV000197750 uncertain significance not specified 2015-01-29 criteria provided, single submitter clinical testing The p.Ile269Thr variant in DSG2 has been reported in 1 individual with ARVC (Fre ssart 2010) and has been identified in 6/11544 of Latino chromosomes by the Exom e Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computational p rediction tools and conservation analysis do not provide strong support for or a gainst an impact to the protein. In summary, the clinical significance of the p. Ile269Thr variant is uncertain.
Invitae RCV001045466 SCV001209319 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-09-22 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 269 of the DSG2 protein (p.Ile269Thr). This variant is present in population databases (rs727502986, gnomAD 0.04%). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 20400443). ClinVar contains an entry for this variant (Variation ID: 163204). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DSG2 protein function. 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.
Color Diagnostics, LLC DBA Color Health RCV001181124 SCV001346210 likely benign Cardiomyopathy 2023-03-09 criteria provided, single submitter clinical testing
GeneDx RCV001563010 SCV001785876 uncertain significance not provided 2021-02-02 criteria provided, single submitter clinical testing Identified in a patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) (Fressart et al., 2010); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 163204; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20400443)
Fulgent Genetics, Fulgent Genetics RCV002478420 SCV002794298 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-08-03 criteria provided, single submitter clinical testing

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.