ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.643C>T (p.Arg215Cys) (rs397516063)

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
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035653 SCV000059304 uncertain significance not specified 2014-06-25 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Ambry Genetics RCV000245767 SCV000320166 uncertain significance Cardiovascular phenotype 2017-04-04 criteria provided, single submitter clinical testing The p.R215C variant (also known as c.643C>T), located in coding exon 5 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 643. The arginine at codon 215 is replaced by cysteine, an amino acid with highly dissimilar properties. A Chinese patient with hypertrophic cardiomyopathy (HCM) was described to have this variant in addition to another alteration in TNNT2 (Zou Y et al. Mol Biol Rep. 2013;40(6):3969-76). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV000463175 SCV000558163 likely benign Hypertrophic cardiomyopathy 2020-09-07 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852654 SCV000995360 likely benign Cardiomyopathy 2018-03-22 criteria provided, single submitter clinical testing
Mendelics RCV000988553 SCV001138317 uncertain significance Familial hypertrophic cardiomyopathy 4 2019-05-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000852654 SCV001352035 uncertain significance Cardiomyopathy 2021-01-13 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 215 of the MYBPC3 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in Chinese individuals affected with hypertrophic cardiomyopathy (PMID: 23283745, 30600190). This variant has also been identified in 28/240996 chromosomes (22/17902 East Asian chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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.