Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV001171158 | SCV001333843 | uncertain significance | Cardiomyopathy | 2018-06-21 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001171158 | SCV001354164 | uncertain significance | Cardiomyopathy | 2023-04-24 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 712 of the PKP2 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 compound heterozygosity with a PKP2 whole gene deletion in two siblings affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 28767663). This variant has been identified in 4/282790 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. |
Invitae | RCV001327219 | SCV001518282 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 712 of the PKP2 protein (p.Gly712Arg). This variant is present in population databases (rs200844640, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 915785). 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"). 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. |