ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2828G>A (p.Arg943Gln)

gnomAD frequency: 0.00003  dbSNP: rs397515986
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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035529 SCV000059179 uncertain significance not specified 2015-09-03 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170197 SCV001332749 uncertain significance Cardiomyopathy 2018-03-28 criteria provided, single submitter clinical testing
Invitae RCV001365207 SCV001561470 uncertain significance Hypertrophic cardiomyopathy 2023-04-10 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 42659). This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy and/or pediatric hypertrophic cardiomyopathy (PMID: 23283745, 27532257, 32746448). This variant is present in population databases (rs397515986, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 943 of the MYBPC3 protein (p.Arg943Gln).
Fulgent Genetics, Fulgent Genetics RCV002477067 SCV002787017 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-07-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV003298046 SCV003989414 uncertain significance Cardiovascular phenotype 2023-03-28 criteria provided, single submitter clinical testing The p.R943Q variant (also known as c.2828G>A), located in coding exon 27 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2828. The arginine at codon 943 is replaced by glutamine, an amino acid with highly similar properties. This variant has been detected in hypertrophic cardiomyopathy (HCM) cohorts or cohorts referred for HCM genetic testing; however, details were limited and reports may overlap (Zou Y et al. Mol Biol Rep, 2013 Jun;40:3969-76; Walsh R et al. Genet Med, 2017 Feb;19:192-203; Burstein DS et al. Pediatr Res, 2021 May;89:1470-1476; Harper AR et al. Nat Genet, 2021 Feb;53:135-142). This variant has also been detected in a sudden death case with presumed epilepsy (Chahal CAA et al. J Am Heart Assoc, 2021 Dec;10:e021170). One study suggested this variant may not significantly impact certain protein binding interactions; however, the physiological relevance of this finding is unclear (Ponnam S et al. J Biol Chem, 2022 Jan;298:101485). 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.

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.