ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.782G>A (p.Arg261His) (rs727502984)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150534 SCV000197748 likely benign not specified 2014-08-07 criteria provided, single submitter clinical testing Arg261His in exon 7 of DSG2: This variant is not expected to have clinical signi ficance due to a lack of conservation across species, including mammals. Of note , 6 mammals (dolphin, killer whale, white rhinoceros, shrew, aardvark, and armad illo) have a histidine (His) at this position despite high nearby amino acid con servation. Additional computational prediction tools do not suggest a high likel ihood of impact to the protein.
Invitae RCV000642316 SCV000763985 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2019-05-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 261 of the DSG2 protein (p.Arg261His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSG2-related disease. ClinVar contains an entry for this variant (Variation ID: 163202). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 Health, Inc RCV001526076 SCV001736352 uncertain significance Cardiomyopathy 2021-01-11 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 261 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 2/248768 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.