ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.2013del (p.Lys672fs) (rs764817683)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183795 SCV000236276 pathogenic not provided 2017-04-12 criteria provided, single submitter clinical testing The c.2013delC pathogenic variant in the PKP2 gene has been reported in multiple individuals with ARVC and has not been observed in more than 500 control chromosomes (Dalal D et al., 2006; den Haan A et al., 2009; Bauce B et al., 2011). This pathogenic variant causes a shift in reading frame starting at codon Lysine 672, changing it to an Arginine, and creating a premature stop codon at position 12 of the new reading frame, denoted p.Lys672ArgfsX12. 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 variants in the PKP2 gene have been reported in association with ARVC. In summary, c.2013delC in the PKP2 gene is interpreted as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000780607 SCV000918022 pathogenic Cardiac arrhythmia 2018-01-02 criteria provided, single submitter clinical testing Variant summary: The PKP2 c.2013delC (p.Lys672ArgfsX12) variant results in a premature termination codon, predicted to cause a truncated or absent PKP2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One truncation downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2197_2202delinsG, p.His733fsX8; ). One in silico tool predicts a damaging outcome for this variant. This variant was found in 2/247018 control chromosomes at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic PKP2 variant (0.0006502). The variant has been reported in numerous affected individuals and families, and has been reported to segregate in families with ARVD, albeit with less than full penetrance (Dalal_2006, Konig_2017, Arbustini_2014). A functional study has shown the variant leads to undetectable mutant cDNA levels indicating instability and degredation (Kim_2013). In addition, one clinical diagnostic laboratory/reputable database classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Color RCV001183812 SCV001349645 pathogenic Cardiomyopathy 2019-03-21 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.