Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001297928 | SCV001486966 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-06-27 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 1001605). This missense change has been observed in individual(s) with clinical features of arrhythmogenic right ventricular cardiomyopathy (PMID: 33460606). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 388 of the DSG2 protein (p.Phe388Cys). |
Baylor Genetics | RCV001335883 | SCV001529137 | uncertain significance | Dilated cardiomyopathy 1BB | 2018-05-16 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Ambry Genetics | RCV002322193 | SCV002628878 | uncertain significance | Cardiovascular phenotype | 2023-12-18 | criteria provided, single submitter | clinical testing | The p.F388C variant (also known as c.1163T>G), located in coding exon 9 of the DSG2 gene, results from a T to G substitution at nucleotide position 1163. The phenylalanine at codon 388 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant co-occurred (in trans) with a second DSG2 variant in an individual reported to have arrhythmogenic right ventricular cardiomyopathy (Scheel PJ et al. Am J Cardiol. 2021 Apr;145:128-134e). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002504441 | SCV002814331 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-07-23 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV003532931 | SCV004363182 | uncertain significance | Cardiomyopathy | 2023-11-13 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with cysteine at codon 388 of the DSG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with myocarditis and arrhythmogenic right ventricular cardiomyopathy (PMID: 33460606). This variant has been identified in 1/249458 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. |