ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.275T>A (p.Leu92Ter) (rs763639737)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183800 SCV000236281 pathogenic not provided 2018-03-30 criteria provided, single submitter clinical testing The L92X variant in the PKP2 gene has been reported in association ARVC (Fressart et al., 2010; Alcade et al., 2014; Walsh et al., 2017). This variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the PKP2 gene have been reported in Human Gene Mutation Database in association with ARVC (Stenson et al., 2014). Furthermore, the L92X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016).
Invitae RCV000463730 SCV000545251 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-09-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 92 (p.Leu92*) of the PKP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853). This particular variant has been reported in the literature in individuals with arrhythmogenic right ventricular cardiomyopathy (PMID: 20400443, 24832006). ClinVar contains an entry for this variant (Variation ID: 202026). For these reasons, this variant has been classified as Pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000463730 SCV000840039 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-05-11 criteria provided, single submitter clinical testing The c.275T>A (p.Leu92*) variant in the PKP2 gene has been detected in two patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) from a cohort of 135 patients. [PMID 20400443 ]. This c.275T>A change creates a premature stop codon at amino acid position 92 of the PKP2 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This c.275T>A (p.Leu92*) variant thus classified as pathogenic.

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