ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.3476C>T (p.Thr1159Met)

gnomAD frequency: 0.00004  dbSNP: rs780305056
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000547212 SCV000648247 uncertain significance Hypertrophic cardiomyopathy 14 2023-05-20 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH6 protein function. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1159 of the MYH6 protein (p.Thr1159Met). This variant is present in population databases (rs780305056, gnomAD 0.003%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy and dilated cardiomyopathy (PMID: 31513939, 32969603). ClinVar contains an entry for this variant (Variation ID: 470525). 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.
Center for Human Genetics, University of Leuven RCV000768515 SCV000886828 uncertain significance Hypertrophic cardiomyopathy 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV002259350 SCV002538840 uncertain significance not provided 2022-06-24 criteria provided, single submitter clinical testing Identified in patients with DCM in the published literature (Carnevale et al., 2020; Robyns et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31513939, 32969603)
Fulgent Genetics, Fulgent Genetics RCV002483463 SCV002804044 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-12-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV003159875 SCV003864564 uncertain significance Cardiovascular phenotype 2023-01-13 criteria provided, single submitter clinical testing The p.T1159M variant (also known as c.3476C>T), located in coding exon 24 of the MYH6 gene, results from a C to T substitution at nucleotide position 3476. The threonine at codon 1159 is replaced by methionine, an amino acid with similar properties. This alteration has been reported in subjects with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) (Carnevale A et al. Mol Genet Genomic Med, 2020 Nov;8:e1504; Robyns T et al. Eur J Med Genet, 2020 Mar;63:103754). 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.