Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002042790 | SCV002294990 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 9 | 2024-06-11 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 6 (c.1442_1510+239del) of the PKP2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 17041889, 23911551). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV002389019 | SCV002697876 | uncertain significance | Cardiovascular phenotype | 2022-09-14 | criteria provided, single submitter | clinical testing | The c.1442_1510+239del308 gross deletion includes at least a portion of coding exon 6 and involves the canonical splice donor site after coding exon 6 of the PKP2 gene. Canonical splice site alterations are typically deleterious in nature, and loss of PKP2 function is an accepted mechanism of disease. However, pathogenicity has not been established for alterations in exon 6 of PKP2. The exon is alternatively spliced, and the predominant isoform in human cardiac tissue, PKP2A, does not include exon 6 (Gandjbakhch E et al. Heart. 2011;97(10):844-9). Since supporting evidence is limited at this time, the clinical significance of this alteration is unclear. |