ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.2090G>T (p.Gly697Val) (rs143503798)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000151652 SCV000199909 uncertain significance not specified 2013-10-14 criteria provided, single submitter clinical testing The Gly741Val variant in PKP2 has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 2/4406 African American chromosome s by the NHLBI Exome Sequencing Project (; dbSN P rs143503798). Computational analyses (biochemical amino acid properties, conse rvation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or ag ainst an impact to the protein. Additional information is needed to fully assess the clinical significance of this variant.
GeneDx RCV000766580 SCV000236292 uncertain significance not provided 2014-11-03 criteria provided, single submitter clinical testing p.Gly741Val (GGT>GTT): c.2222 G>T in exon 11 of the PKP2 gene (NM_004572.3). The G741V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G741V variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is conserved within mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, the G741V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, no definitive missense mutations in nearby residues have been reported. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Invitae RCV001053441 SCV001217701 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 9 2019-12-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 741 of the PKP2 protein (p.Gly741Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs143503798, ExAC 0.01%). This variant has not been reported in the literature in individuals with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 164953). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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