Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001179092 | SCV001343685 | uncertain significance | Cardiomyopathy | 2023-04-07 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 198 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with sporadic dilated cardiomyopathy (PMID: 34486814). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001875922 | SCV002158672 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 198 of the PKP2 protein (p.Glu198Lys). 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. ClinVar contains an entry for this variant (Variation ID: 920375). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Ambry Genetics | RCV003293932 | SCV003996550 | uncertain significance | Cardiovascular phenotype | 2023-03-28 | criteria provided, single submitter | clinical testing | The p.E198K variant (also known as c.592G>A), located in coding exon 3 of the PKP2 gene, results from a G to A substitution at nucleotide position 592. The glutamic acid at codon 198 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Saito T et al. ESC Heart Fail, 2021 Dec;8:5178-5191). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |