ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2631G>T (p.Met877Ile)

dbSNP: rs1060505018
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
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001197233 SCV001367870 likely pathogenic Congenital myopathy with fiber type disproportion 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP2,PP3.
Invitae RCV000477668 SCV001576910 pathogenic Hypertrophic cardiomyopathy 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 877 of the MYH7 protein (p.Met877Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 27532257, 27737317, 28699631). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 417718). 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 MYH7 protein function with a positive predictive value of 80%. This variant disrupts the p.Met877 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11133230). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genetics and Molecular Pathology, SA Pathology RCV002466513 SCV002761860 likely pathogenic Hypertrophic cardiomyopathy 1 2021-07-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023097 SCV004943778 uncertain significance Cardiovascular phenotype 2020-07-22 criteria provided, single submitter clinical testing The c.2631G>T (p.M877I) alteration is located in exon 22 (coding exon 20) of the MYH7 gene. This alteration results from a G to T substitution at nucleotide position 2631, causing the methionine (M) at amino acid position 877 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Rampazzo Lab, Human Molecular Genetics Unit, University of Padua RCV000477668 SCV000564076 pathogenic Hypertrophic cardiomyopathy 2017-04-18 no assertion criteria provided research More HCM patients from different families carrying this variation. This variant is absent in different population databases (dbSNP , Exome Aggregation Consortium ; 1000 Genomes Project and Exome Variant Server) moreover it involves a highly conserved residue in subfragment 2 domain of the neck region of the myosin protein.

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.