ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1939_1961del (p.Cys647fs) (rs1555142963)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769390 SCV000900782 likely pathogenic Cardiomyopathy 2017-02-09 criteria provided, single submitter clinical testing
GeneDx RCV000484299 SCV000573037 likely pathogenic not provided 2018-11-06 criteria provided, single submitter clinical testing Although the c.1939_1961del23 likely pathogenic variant in the PKP2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon cysteine 647, changing it to a serine, and creating a premature stop codon at position 88 of the new reading frame, denoted p.C647SfsX88. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Many other frameshift variants in the PKP2 gene have been reported in Human Gene Mutation Database in association with ARVC (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.1939_1961del23 variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).In summary, c.1939_1961del23 in the PKP2 gene is interpreted as a likely pathogenic variant.

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