Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000221231 | SCV000272307 | uncertain significance | not specified | 2014-12-30 | criteria provided, single submitter | clinical testing | The p.Ser53Arg variant in PKP2 has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 1/46846 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computat ional prediction tools and conservation analysis do not provide strong evidence for or against an impact to the protein. In summary, the clinical significance o f the p.Ser53Arg variant is uncertain. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769399 | SCV000900791 | uncertain significance | Cardiomyopathy | 2015-09-29 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001340993 | SCV001534830 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2020-10-07 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 229144). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces serine with arginine at codon 53 of the PKP2 protein (p.Ser53Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. |