Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001190097 | SCV001357512 | uncertain significance | Cardiomyopathy | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 739 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 been reported in an individual affected with dilated cardiomyopathy (PMID: 31983221). This variant has been identified in 2/249390 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 |
RCV001863011 | SCV002205049 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-03-18 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 739 of the DSG2 protein (p.Ile739Val). This variant is present in population databases (rs772240008, gnomAD 0.002%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 927083). 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Ambry Genetics | RCV002429836 | SCV002730838 | uncertain significance | Cardiovascular phenotype | 2021-10-20 | criteria provided, single submitter | clinical testing | The p.I739V variant (also known as c.2215A>G), located in coding exon 14 of the DSG2 gene, results from an A to G substitution at nucleotide position 2215. The isoleucine at codon 739 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is poorly 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, |
RCV004010408 | SCV004821768 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2024-06-11 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 739 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 been reported in an individual affected with dilated cardiomyopathy (PMID: 31983221). This variant has been identified in 2/249390 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. |