Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000604904 | SCV000731567 | likely pathogenic | Cardiomyopathy | 2017-04-28 | criteria provided, single submitter | clinical testing | The p.Gly560fs variant in PKP2 has not been previously reported in individuals w ith cardiomyopathy or in large population studies, though the ability of these s tudies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 560 and leads to a premature termination codon 12 amino acids downstrea m. This alteration is then predicted to lead to a truncated or absent protein. F rameshift and other truncating variants in PKP2 are strongly associated with arr hythmogenic right ventricular cardiomyopathy. In summary, although additional st udies are required to fully establish its clinical significance, the p.Gly560fs variant is likely pathogenic. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678352 | SCV000804416 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 9 | 2017-11-27 | criteria provided, single submitter | provider interpretation | This 6 year old male with autism spectrum disorder was found to carry a paternally-inherited expected pathogenic variant in the PKP2 gene, which confers an increased risk of developing arrhythmogenic right ventricular cardiomyopathy. Given his age, we would not expect him to exhibit any features of the condition at this time, though a cardiac evaluation is pending. The patient's father's cardiac MRI has thus far been normal; he is 31 years old at time of report and cardiac evaluation. |
| Invitae | RCV000678352 | SCV000946376 | pathogenic | Arrhythmogenic right ventricular dysplasia 9 | 2019-10-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly560Trpfs*12) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). This variant has not been reported in the literature in individuals with PKP2-related disease. ClinVar contains an entry for this variant (Variation ID: 517335). This variant is not present in population databases (ExAC no frequency). |