Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001190545 | SCV001358050 | likely benign | Cardiomyopathy | 2019-03-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001231103 | SCV001403608 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 10 of the PKP2 protein (p.Tyr10Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with PKP2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |