ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.2017C>T (p.Pro673Ser)

gnomAD frequency: 0.00001  dbSNP: rs757205704
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001958558 SCV002217611 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2023-09-22 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1446648). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 717 of the PKP2 protein (p.Pro717Ser). This variant is present in population databases (rs757205704, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. 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 RCV003170113 SCV003912858 uncertain significance Cardiovascular phenotype 2023-02-10 criteria provided, single submitter clinical testing The p.P717S variant (also known as c.2149C>T), located in coding exon 11 of the PKP2 gene, results from a C to T substitution at nucleotide position 2149. The proline at codon 717 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV003533075 SCV004358857 uncertain significance Cardiomyopathy 2021-10-21 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 717 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/251252 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.

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