ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2927C>G (p.Pro976Arg)

gnomAD frequency: 0.00001  dbSNP: rs954096716
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
Ambry Genetics RCV002438611 SCV002748754 uncertain significance Cardiovascular phenotype 2022-06-16 criteria provided, single submitter clinical testing The p.P976R variant (also known as c.2927C>G), located in coding exon 28 of the MYBPC3 gene, results from a C to G substitution at nucleotide position 2927. The proline at codon 976 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in one subject with hypertrophic cardiomyopathy (HCM) (Waldmüller S et al. Eur. J. Heart Fail., 2011 Nov;13:1185-92). This variant was also detected in a cardiomyopathy genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). 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 alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002498993 SCV002813380 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-10-29 criteria provided, single submitter clinical testing
Invitae RCV002531732 SCV003276625 uncertain significance Hypertrophic cardiomyopathy 2022-10-14 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 518241). This missense change has been observed in individual(s) with clinical features of MYBPC3-related conditions (PMID: 21750094, 30847666). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 976 of the MYBPC3 protein (p.Pro976Arg).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000600797 SCV000733031 uncertain significance Hypertrophic cardiomyopathy 4 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001700238 SCV001921575 uncertain significance not provided no assertion criteria provided 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.