ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2399G>A (p.Gly800Glu)

gnomAD frequency: 0.00001  dbSNP: rs1273374175
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
Color Diagnostics, LLC DBA Color Health RCV001178392 SCV001342830 uncertain significance Cardiomyopathy 2023-09-13 criteria provided, single submitter clinical testing This missense variant replaces glycine with glutamic acid at codon 800 of the MYBPC3 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001773423 SCV001991967 uncertain significance not provided 2019-04-11 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002480601 SCV002775701 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-10-09 criteria provided, single submitter clinical testing
Invitae RCV002558877 SCV003476606 uncertain significance Hypertrophic cardiomyopathy 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 800 of the MYBPC3 protein (p.Gly800Glu). This variant is not present in population databases (gnomAD no frequency). 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: 919921). 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. 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.
Ambry Genetics RCV003293928 SCV004001260 uncertain significance Cardiovascular phenotype 2023-04-28 criteria provided, single submitter clinical testing The p.G800E variant (also known as c.2399G>A), located in coding exon 24 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2399. The glycine at codon 800 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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.