ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1170+2T>A (rs397516987)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038150 SCV000061816 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2013-02-20 criteria provided, single submitter clinical testing The 1170+2T>A variant in PKP2 has not been reported in the literature, but has b een identified by our laboratory in 1 individual with ARVC and segregated with d isease in 1 affected relative (LMM unpublished data). This variant has also not been identified in large European American and African American populations by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS), which incr eases the likelihood that it is pathogenic. However, we cannot exclude that it m ay be common in other populations. This variant occurs in the invariant region ( +/- 1,2) of the splice consensus sequence and is predicted to cause altered spli cing leading to an abnormal or absent protein. In summary, this variant is likel y to be pathogenic, though additional studies are required to fully establish it s clinical significance.
GeneDx RCV000183737 SCV000236217 pathogenic not provided 2012-08-09 criteria provided, single submitter clinical testing c.1170+2 T>A: IVS4+2 T>A in intron 4 of the PKP2 gene (NM_004572.3). Although the c.1170+2 T>A mutation has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge, this mutation destroys the canonical splice donor site in intron 4 and is predicted to cause abnormal gene splicing. The mutation is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site mutations in the PKP2 gene have been reported in association with ARVC. In summary, c.1170+2 T>A in the PKP2 gene is interpreted as a disease-causing mutation. The variant is found in ARVC panel(s).

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