Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001294542 | SCV001483423 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 785 of the DSC2 protein (p.Glu785Gly). 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. 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 expected to disrupt DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 998654). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). This variant is present in population databases (rs769747496, gnomAD 0.003%). |
Color Diagnostics, |
RCV001806098 | SCV002053543 | uncertain significance | Cardiomyopathy | 2023-05-01 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 785 of the DSC2 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 3/251122 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 | RCV002447262 | SCV002733624 | uncertain significance | Cardiovascular phenotype | 2019-10-18 | criteria provided, single submitter | clinical testing | The p.E785G variant (also known as c.2354A>G), located in coding exon 15 of the DSC2 gene, results from an A to G substitution at nucleotide position 2354. The glutamic acid at codon 785 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004004954 | SCV004816063 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 785 of the DSC2 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 3/251122 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. |