ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1045G>A (p.Asp349Asn)

gnomAD frequency: 0.00001  dbSNP: rs754281384
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
Labcorp Genetics (formerly Invitae), Labcorp RCV002002884 SCV002275360 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2021-12-27 criteria provided, single submitter clinical testing 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. 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 asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs754281384, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 349 of the DSG2 protein (p.Asp349Asn).
Ambry Genetics RCV002398050 SCV002704975 uncertain significance Cardiovascular phenotype 2021-08-02 criteria provided, single submitter clinical testing The p.D349N variant (also known as c.1045G>A), located in coding exon 9 of the DSG2 gene, results from a G to A substitution at nucleotide position 1045. The aspartic acid at codon 349 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004011053 SCV004817227 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 349 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 2/249264 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.