Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000037263 | SCV000060920 | uncertain significance | not specified | 2013-01-23 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Asp402Asn varia nt in DSG2 has not been reported in the literature nor previously identified by our laboratory. This variant has also not been identified in large European Amer ican and African American populations by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS), though it may be common in other populations. As partic acid (Asp) at position 402 is poorly conserved in evolution with 1 mammal ian species carrying the variant amino acid (asparagine), suggesting that a chan ge may be tolerated. Other computational analyses (biochemical amino acid prope rties, AlignGVGD, PolyPhen2, and SIFT) suggest that the Asp402Asn variant may no t impact the protein, though this information is not predictive enough to rule o ut pathogenicity. Although this data supports that the Asp402Asn variant may be benign, additional studies are needed to fully assess its clinical significance. |
Illumina Laboratory Services, |
RCV001125523 | SCV001284599 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Color Diagnostics, |
RCV001525531 | SCV001735671 | uncertain significance | Cardiomyopathy | 2022-02-03 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 402 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 10/249400 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. |
Gene |
RCV001770058 | SCV001994016 | uncertain significance | not provided | 2019-07-03 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Labcorp Genetics |
RCV001125523 | SCV002290813 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2024-01-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 402 of the DSG2 protein (p.Asp402Asn). This variant is present in population databases (rs397516701, 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: 44279). 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 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. |
Ambry Genetics | RCV004018832 | SCV004859457 | benign | Cardiovascular phenotype | 2024-03-18 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |