Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000774476 | SCV000908179 | likely benign | Cardiomyopathy | 2022-06-08 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001001976 | SCV001159784 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2018-07-18 | criteria provided, single submitter | clinical testing | The PKP2 c.983G>C; p.Gly328Ala variant (rs144651139), to our knowledge, is not reported in the medical literature. This variant is found in the general population with an overall allele frequency of 0.007% (19/275864 alleles) in the Genome Aggregation Database. The glycine at codon 328 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to the absence of clinical and functional information, the clinical significance of the p.Gly328Ala variant is uncertain at this time. |
| Labcorp Genetics |
RCV001001976 | SCV001200863 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 328 of the PKP2 protein (p.Gly328Ala). This variant is present in population databases (rs144651139, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 629764). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Gene |
RCV002282364 | SCV002571675 | uncertain significance | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
| Ambry Genetics | RCV002386344 | SCV002695732 | likely benign | Cardiovascular phenotype | 2021-09-01 | 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. |