ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1125_1132del (p.Phe376fs) (rs794729124)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183786 SCV000236267 pathogenic not provided 2012-10-10 criteria provided, single submitter clinical testing Although the c.1125_1132del TTTCATAC variant in the PKP2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Phenylalanine 376, changing it to a Alanine, and creating a premature stop codon at position 8 of the new reading frame, denoted p.Phe376AlafsX8. This variant 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 variant in the PKP2 gene have been reported in association with ARVC. In summary, c.1125_1132del TTTCATAC in the PKP2 gene is interpreted as a pathogenic variant.
Invitae RCV000477267 SCV000545227 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2016-12-19 criteria provided, single submitter clinical testing This sequence change deletes 8 nucleotide from exon 4 of the PKP2 mRNA (c.1125_1132delTTTCATAC), causing a frameshift at codon 376. This creates a premature translational stop signal (p.Phe376Alafs*8) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in PKP2 are known to be pathogenic (PMID: 23911551, 15489853). For these reasons, this variant has been classified as Pathogenic.

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