Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001176257 | SCV001340149 | uncertain significance | Cardiomyopathy | 2020-01-08 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 305 of the DSG2 protein. Computational prediction tool 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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 |
RCV001875803 | SCV002206993 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2021-05-11 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 918592). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 305 of the DSG2 protein (p.Asn305Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. 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. |
| Fulgent Genetics, |
RCV002483949 | SCV002781637 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-10-12 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004000332 | SCV004819496 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 305 of the DSG2 protein. Computational prediction tool 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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. |