Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001182305 | SCV001347710 | likely benign | Cardiomyopathy | 2018-11-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193944 | SCV001363123 | uncertain significance | not specified | 2019-10-08 | criteria provided, single submitter | clinical testing | Variant summary: PKP2 c.2145A>G (p.Pro715Pro) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251390 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2145A>G in individuals affected with Arrhythmia/ARVD/SCD/Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
| Ambry Genetics | RCV002429815 | SCV002730294 | likely benign | Cardiovascular phenotype | 2020-08-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV003617903 | SCV004524442 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2023-06-24 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 922293). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 715 of the PKP2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PKP2 protein. It affects a nucleotide within the consensus splice site. |