ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.2499C>A (p.His833Gln)

dbSNP: rs202094467
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172083 SCV000051031 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000219286 SCV000272309 uncertain significance not specified 2015-06-25 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.His877Gln var iant in PKP2 has been reported in 1 adult with DCM who also carried a likely pat hogenic splice variant in the DSP gene (Elliott 2010). This variant has also bee n identified in 0.1% (21/16512) of South Asian chromosomes including one homozyg ote by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs202094467). Computational prediction tools and conservation analysis do n ot provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.His877Gln variant is uncertain, its fre quency suggests that it is more likely to be benign.
Color Diagnostics, LLC DBA Color Health RCV000771962 SCV000904916 likely benign Cardiomyopathy 2020-04-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001429984 SCV001632707 likely benign Arrhythmogenic right ventricular dysplasia 9 2024-01-28 criteria provided, single submitter clinical testing
GeneDx RCV000172083 SCV001818648 likely benign not provided 2021-06-02 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20716751)
Ambry Genetics RCV002426820 SCV002744732 uncertain significance Cardiovascular phenotype 2021-05-17 criteria provided, single submitter clinical testing The p.H877Q variant (also known as c.2631C>A), located in coding exon 14 of the PKP2 gene, results from a C to A substitution at nucleotide position 2631. The histidine at codon 877 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort; however, this individual was also identified to have another alteration in a different cardiac-related gene (Elliott P et al. Circ Cardiovasc Genet, 2010 Aug;3:314-22). Additionally, this alteration has been reported as a secondary cardiac variant in an exome cohort with limited clinical details (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.