ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.623del (p.Thr208fs) (rs794729122)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000505720 SCV000236264 pathogenic not provided 2018-09-14 criteria provided, single submitter clinical testing The c.623delC pathogenic variant in the PKP2 gene has not been published as a pathogenic variant or reported as a benign variant to our knowledge. Furthermore, the c.623delC pathogenic variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This pathogenic variant causes a shift in reading frame starting at codon Threonine 208, changing it to a Lysine, and creating a premature stop codon at position 55 of the new reading frame, denoted p.Thr208LysfsX55. The c.623delC variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. In addition, other frameshift variants in the PKP2 gene have been reported in the Human Gene Mutation Database in association with ARVC and sudden unexpected death (Stenson et al., 2014).
Invitae RCV000640014 SCV000761601 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-03-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr208Lysfs*55) 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 disease. ClinVar contains an entry for this variant (Variation ID: 202013). 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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