ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.772A>T (p.Lys258Ter) (rs727504430)

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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 RCV000154661 SCV000204338 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2013-01-04 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000183803 SCV000236284 pathogenic not provided 2014-09-05 criteria provided, single submitter clinical testing p.Lys258Ter (AAG>TAG): c.772 A>T in exon 3 of the PKP2 gene (NM_004572.3). The K258X mutation in the PKP2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. K258X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense mutations in the PKP2 gene have been reported in association with arrhythmogenic right ventricular cardiomyopathy. Additionally, the K258X mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, K258X in the PKP2 gene is interpreted as a disease-causing mutation. The variant is found in CARDIOMYOPATHY panel(s).
Invitae RCV001237410 SCV001410169 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2019-07-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys258*) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 177984). Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). For these reasons, this variant has been classified as Pathogenic.

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