Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Servicio Canario de Salud, |
RCV003447429 | SCV004174269 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 9 | 2023-12-06 | criteria provided, single submitter | clinical testing | The c.1841T>C p.(Leu614Pro) PKP2 variant has been reported in our laboratory in a 58-year-old female patient with a clinical diagnosis of arrhythmogenic right ventricular dysplasia. Pacemaker carrier. Permanent atrial fibrillation. Sister died of sudden death at the age of 19 during sports activity, another brother died of sudden death at the age of 19 while dancing. This variant has never been reported in PKP2 related-disorders. This variant was absent from large population studies (gnomAD no frequency). In summary, the available evidence for c.1841T>C p.(Leu614Pro) PKP2 variant meets our criteria to be classified as Likely Pathogenic based upon its absence from controls and the clinical correlation in this patient´s phenotype. |
| Labcorp Genetics |
RCV003447429 | SCV004295866 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 614 of the PKP2 protein (p.Leu614Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with arrhythmogenic right ventricular cardiomyopathy (PMID: 22798562; Invitae). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |