ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1170+5G>A (rs794729105)

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 RCV000183739 SCV000236219 uncertain significance not provided 2014-10-13 criteria provided, single submitter clinical testing c.1170+5 G>A: IVS4+5 G>A in intron 4 of the PKP2 gene (NM_004572.3). The c.1170+5 G>A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.1170+5 G>A 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. Other splice site mutations in the PKP2 gene have been reported in association with ARVC. However, in silico splice site prediction algorithms are inconsistent in their predictions as to whether or not the variant impacts the splice donor site in intron 4 of the PKP2 gene. At least one splice prediction algorithm predicts c.1170+5 G>A destroys or reduces the efficiency of the splice donor site, which may lead to abnormal gene splicing. However, another splice prediction algorithm predicts only minimal reduction in splice donor site efficiency. 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 ARVC panel(s).
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170220 SCV001332778 uncertain significance Cardiomyopathy 2018-07-31 criteria provided, single submitter clinical testing
Color RCV001170220 SCV001346237 uncertain significance Cardiomyopathy 2019-06-22 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.