ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2690C>A (p.Ala897Asp)

gnomAD frequency: 0.00001  dbSNP: rs765238150
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
GeneDx RCV000181232 SCV000233511 uncertain significance not provided 2013-01-16 criteria provided, single submitter clinical testing p.Ala897Asp (GCC>GAC): c.2690 C>A in exon 15 of the DSG2 gene (NM_001943.3). The Ala897Asp variant in the DSG2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ala897Asp results in a non-conservative amino acid substitution of a non-polar Alanine with a negatively charged Aspartic acid at a position that is not uniformly conserved across species. The Ala897Asp variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, in silico analysis predicts Ala897Asp is benign to the protein structure/function. Additionally, no mutations in nearby codons have been reported in association with ARVC. With the information available at this time, we cannot definitively determine if Ala897Asp is a disease-causing mutation or a rare benign variant. The variant is found in ARVC panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000796747 SCV000936273 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-09-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 897 of the DSG2 protein (p.Ala897Asp). This variant is present in population databases (rs765238150, gnomAD 0.005%). 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: 199818). 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 RCV001526107 SCV001736392 uncertain significance Cardiomyopathy 2023-08-23 criteria provided, single submitter clinical testing This missense variant replaces alanine with aspartic acid at codon 897 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 9/280358 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 RCV002453645 SCV002739778 uncertain significance Cardiovascular phenotype 2019-03-07 criteria provided, single submitter clinical testing The p.A897D variant (also known as c.2690C>A), located in coding exon 15 of the DSG2 gene, results from a C to A substitution at nucleotide position 2690. The alanine at codon 897 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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 RCV003996623 SCV004821824 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces alanine with aspartic acid at codon 897 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 9/280358 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.