ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2162A>G (p.His721Arg)

gnomAD frequency: 0.00003  dbSNP: rs756912703
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000265529 SCV000408241 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000304243 SCV000408242 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000804791 SCV000944718 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 721 of the DSG2 protein (p.His721Arg). This variant is present in population databases (rs756912703, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 326483). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DSG2 protein function with a negative predictive value of 95%. 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 RCV001188866 SCV001356024 uncertain significance Cardiomyopathy 2023-05-02 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 721 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSG2-related disorders in the literature. This variant has been identified in 9/249448 chromosomes 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.
Ambry Genetics RCV002418187 SCV002724692 likely benign Cardiovascular phenotype 2023-03-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity RCV003144213 SCV003829132 uncertain significance not provided 2022-05-27 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000304243 SCV004821759 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 721 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 9/249448 chromosomes 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.

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.