Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000208434 | SCV000263856 | uncertain significance | Cardiac arrest | 2015-02-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001192093 | SCV001360065 | uncertain significance | Cardiomyopathy | 2023-04-21 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 730 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 1/249442 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. |
Labcorp Genetics |
RCV001371736 | SCV001568315 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 730 of the DSG2 protein (p.Thr730Ala). 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 alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 222564). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs780650226, gnomAD 0.0009%). |
Ambry Genetics | RCV003298271 | SCV003996712 | uncertain significance | Cardiovascular phenotype | 2023-06-11 | criteria provided, single submitter | clinical testing | The p.T730A variant (also known as c.2188A>G), located in coding exon 14 of the DSG2 gene, results from an A to G substitution at nucleotide position 2188. The threonine at codon 730 is replaced by alanine, an amino acid with 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, |
RCV003997674 | SCV004821764 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2024-08-13 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 730 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 1/249442 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. |