ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1708del (p.Leu570fs)

dbSNP: rs1555142994
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588591 SCV000698467 likely pathogenic Familial isolated arrhythmogenic right ventricular dysplasia 2016-05-10 criteria provided, single submitter clinical testing Variant summary: The PKP2 c.1840delC (p.Leu614Serfs) variant causes a frameshift mutation resulting in a premature termination codon, a known mechanism for disease, as these types of variants are predicted to cause transcript degradation through nonsense mediated decay or produce a truncated protein. Truncations and frameshifts downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Ser837fs). The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications and/or reputable databases/clinical laboratories. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as a Likely Pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000604450 SCV000711728 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2016-01-26 criteria provided, single submitter clinical testing The p.Leu614fs variant in PKP2 has not been previously reported in individuals w ith cardiomyopathy or in large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 614 and leads to a premature termination codon 42 amino acids downstrea m. This alteration is then predicted to lead to a truncated or absent protein. H eterozygous loss of function of the PKP2 gene is an established disease mechanis m in individuals with arrhythmogenic right ventricular cardiomyopathy. In summar y, although additional studies are required to fully establish its clinical sign ificance, the p.Leu614fs variant is likely pathogenic.

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