ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.369G>A (p.Trp123Ter) (rs774663443)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183724 SCV000236202 pathogenic not provided 2017-02-01 criteria provided, single submitter clinical testing p.Trp123Stop (TGG>TGA):c.369 G>A in exon 3 of the PKP2 gene (NM_004572.3). The Trp123Stop mutation in the PKP2 gene has been reported in association with ARVC (Aneq M et al., 2012). Trp123Stop is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense mutations in the PKP2 gene have been reported in association with ARVC. In summary, Trp123Stop in the PKP2 gene is interpreted as a disease-causing mutation. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is primarily an autosomal dominant disease characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death (McNally E et al., 2009; Nava A et al., 2000). ARVC is most frequently caused by mutations in the genes encoding desmosomal proteins, complexes that maintain cell-to-cell connections and provide mechanical attachments among adjacent cells. Less commonly, ARVC may be caused by mutations in genes that encode proteins that maintain calcium homeostasis (McNally E et al., 2009). At least 11% of patients with autosomal dominant arrhythmogenic right ventricular cardiomyopathy were reported to have a mutation in the PKP2 gene (McNally E et al., 2009). The variant is found in ARVC panel(s).
Ambry Genetics RCV000621084 SCV000734938 pathogenic Cardiovascular phenotype 2017-11-09 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV001068398 SCV001233510 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2019-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp123*) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs774663443, ExAC 0.002%). This nonsense change has been observed in individual(s) with clinical features of arrhythmogenic right ventricular cardiomyopathy (PMID: 28600387, 22035158). ClinVar contains an entry for this variant (Variation ID: 201970). Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000183724 SCV001250085 pathogenic not provided 2018-06-01 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.