ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1803del (p.Asp601fs) (rs794729129)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183794 SCV000236275 pathogenic not provided 2014-05-30 criteria provided, single submitter clinical testing p.Asp601GlufsX55 (D601EfsX55): c.1803delC in exon 8 of the PKP2 gene (NM_004572.3). The normal sequence with the base that is deleted in braces is: ATGA{C}AAGG. The c.1803delC mutation in the PKP2 gene has been reported previously in one individual diagnosed with ARVC who had a relative with autopsy-confirmed ARVC (Klauke B et al., 2010). This mutation causes a shift in reading frame starting at codon Aspartic acid 601, changing it to a Glutamic Acid, and creating a premature stop codon at position 55 of the new reading frame, denoted p.Asp601GlufsX55. This mutation is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift mutations in the PKP2 gene have been reported in association with ARVC. The variant is found in PKP2 panel(s).
Invitae RCV000794298 SCV000933696 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2019-02-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp601Glufs*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 been observed in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 20829228). ClinVar contains an entry for this variant (Variation ID: 202021). 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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