ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1063C>T (p.Arg355Ter) (rs754912778)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183731 SCV000236211 pathogenic not provided 2015-12-15 criteria provided, single submitter clinical testing p.Arg355Stop (CGA>TGA): c.1063 C>T in exon 4 of the PKP2 gene (NM_004572.3).The R355X mutation in the PKP2 gene has been reported in one individual with ARVC and was absent from 300 healthy control individuals (Bao et al., 2013). R355X 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 ARVC. Furthermore, the R355X 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. The variant is found in ARVC panel(s).
Invitae RCV001218972 SCV001390884 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2019-07-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg355*) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs754912778, ExAC 0.01%). This variant has been observed in individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 24125834, 27532257, 25765472). ClinVar contains an entry for this variant (Variation ID: 201977). 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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