ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2956A>G (p.Lys986Glu)

dbSNP: rs876657871
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
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 RCV000214322 SCV000271992 uncertain significance not specified 2015-03-12 criteria provided, single submitter clinical testing The p.Lys986Glu variant in MYBPC3 has not been previously reported in individual s with cardiomyopathy. Data from large population studies are insufficient to de termine its frequency. Lysine (Lys) at position 986 is not conserved in mammals or evolutionarily distant species and the change to glutamic acid (Glu) was pre dicted to be benign using a computational tool clinically validated by our labor atory. This tool's benign prediction is estimated to be correct 89% of the time (Jordan 2011). In summary, the clinical significance of the p.Lys986Glu variant is uncertain.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV001256765 SCV001433204 uncertain significance Dilated cardiomyopathy 1A 2019-10-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV004020623 SCV005033676 uncertain significance Cardiovascular phenotype 2023-11-03 criteria provided, single submitter clinical testing The p.K986E variant (also known as c.2956A>G), located in coding exon 28 of the MYBPC3 gene, results from an A to G substitution at nucleotide position 2956. The lysine at codon 986 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been reported in a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Harper AR et al. Nat Genet, 2021 Feb;53:135-142). This amino acid position is not 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005090070 SCV005776295 uncertain significance Hypertrophic cardiomyopathy 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 986 of the MYBPC3 protein (p.Lys986Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 228868). 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 tolerated. 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.

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.