ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1744C>T (p.Leu582Phe) (rs794729134)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183807 SCV000236289 uncertain significance not provided 2014-09-03 criteria provided, single submitter clinical testing p.Leu582Phe (CTC>TTC): c.1744 C>T in exon 8 of the PKP2 gene (NM_004572.3). The L582F variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The L582F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, the L582F variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (V587I, I583M) have been reported in association with ARVC. The I583M variant was harbored by a patient with ARVC and it was absent from 300 control patients; however, no segregation studies of the variant were performed ( Bao et al., 2013). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).

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