ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1809T>G (p.Ile603Met)

gnomAD frequency: 0.00001  dbSNP: rs774348756
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001039165 SCV001202679 uncertain significance Hypertrophic cardiomyopathy 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 603 of the MYBPC3 protein (p.Ile603Met). This variant is present in population databases (rs774348756, gnomAD 0.002%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 30297972). ClinVar contains an entry for this variant (Variation ID: 837763). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (PMID: 32034629). 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001799030 SCV002042145 uncertain significance Cardiomyopathy 2020-12-16 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002481870 SCV002784247 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-08-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV004031092 SCV005033728 uncertain significance Cardiovascular phenotype 2023-09-29 criteria provided, single submitter clinical testing The p.I603M variant (also known as c.1809T>G), located in coding exon 19 of the MYBPC3 gene, results from a T to G substitution at nucleotide position 1809. The isoleucine at codon 603 is replaced by methionine, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort and in an exome sequencing cohort (Ho CY et al. Circulation, 2018 Oct;138:1387-1398; Park J et al. Nat Med, 2021 Jan;27:66-72). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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.