Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018334 | SCV004847963 | likely pathogenic | Arrhythmogenic right ventricular cardiomyopathy | 2016-05-06 | criteria provided, single submitter | clinical testing | The p.Gly5fs (c.12delC) variant in PKP2 has not been previously reported, although the p.Gly5fs (c.14delG) variant has been identified in one individual with ARVC (LMM unpublished data). Data from large population studies is insufficient to assess the frequency of this variant. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 5 and lead to a premature termination codon 34 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of PKP2 function is an established disease mechanism in individuals with ARVC. In summary, although additional studies are required to fully establish its clinical significance, the p.Gly5fs variant is likely pathogenic. |