Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000038205 | SCV000061873 | likely pathogenic | Arrhythmogenic right ventricular cardiomyopathy | 2017-04-07 | criteria provided, single submitter | clinical testing | The p.Pro779fs variant in PKP2 has been identified by our laboratory in 1 Caucas ian individual with ARVC. It was absent from large population studies. This vari ant is predicted to cause a frameshift, which alters the protein?s amino acid se quence beginning at position 779 and leads to a premature termination codon 21 a mino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Frameshift and other truncating variants in PKP2 are well-rep orted in individuals with ARVC (ARVD/C Genetic Variant Database, http://arvcdata base.info; Human Gene Mutation Database). In summary, although additional studie s are required to fully establish its clinical significance, the p.Pro779fs vari ant is likely pathogenic. |
| Invitae | RCV001246063 | SCV001419396 | pathogenic | Arrhythmogenic right ventricular dysplasia 9 | 2019-11-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro779Serfs*21) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 45065). Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). For these reasons, this variant has been classified as Pathogenic. |