Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001342556 | SCV001536498 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2020-03-09 | 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. 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 been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 18632414). However, in that individual pathogenic allele[s] were also identified in DSG2, which suggests that this c.988A>G variant was not the primary cause of disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 330 of the DSG2 protein (p.Asn330Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. |
Color Diagnostics, |
RCV003532958 | SCV004363177 | uncertain significance | Cardiomyopathy | 2022-10-11 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 330 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 arrhythmogenic right ventricular dysplasia (PMID 18632414). 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. |