Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001177657 | SCV001341906 | uncertain significance | Cardiomyopathy | 2023-02-02 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with glycine at codon 693 of the PKP2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251386 chromosomes 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 | RCV001241007 | SCV001413996 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 693 of the PKP2 protein (p.Ser693Gly). This variant is present in population databases (rs375295635, gnomAD 0.002%). This missense change has been observed in individual(s) with PKP2-related conditions (PMID: 29540472, 32880476). ClinVar contains an entry for this variant (Variation ID: 919450). 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. |
Ai |
RCV002223273 | SCV002501057 | uncertain significance | not provided | 2022-01-18 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002418611 | SCV002727741 | uncertain significance | Cardiovascular phenotype | 2022-09-25 | criteria provided, single submitter | clinical testing | The p.S693G variant (also known as c.2077A>G), located in coding exon 10 of the PKP2 gene, results from an A to G substitution at nucleotide position 2077. The serine at codon 693 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a cardiomyopathy cohort; however, clinical details were limited (Hazebroek MR et al. Circ Heart Fail, 2018 03;11:e004682). 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. |