ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.663C>A (p.Tyr221Ter) (rs767987619)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183730 SCV000236210 pathogenic not provided 2018-06-29 criteria provided, single submitter clinical testing The Y221X variant in the PKP2 gene has been reported previously in association with ARVC (Rigato et al., 2013; van der Zwaag et al., 2009; Groeneweg et al., 2015; Walsh et al., 2017). Rigato et al. (2013) identified the Y221X variant in one individual who also carried a variant in the DSP gene and was borderline for the task force criteria for ARVC. The Y221X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the PKP2 gene have been reported in Human Gene Mutation Database in association with ARVC (Stenson et al., 2014). Furthermore, the Y221X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000183730 SCV000707036 pathogenic not provided 2017-04-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620046 SCV000736941 pathogenic Cardiovascular phenotype 2017-10-19 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Baylor Genetics RCV000592966 SCV000807273 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2017-09-01 criteria provided, single submitter clinical testing This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory maternally inherited in a 1-year-old male with hypertrophic and dilated cardiomyopathy, heart failure, osteoporosis, hepatomegaly
Invitae RCV000592966 SCV000818311 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2018-07-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr221*) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs767987619, ExAC 0.01%). This variant has been observed in several individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 23889974, 24070718, 27532257) and in a case of sudden unexplained death (PMID: 29247119). ClinVar contains an entry for this variant (Variation ID: 201976). Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). For these reasons, this variant has been classified as Pathogenic.

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.