ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2791G>A (p.Glu931Lys)

dbSNP: rs1131691514
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493293 SCV000582277 likely pathogenic not provided 2015-09-16 criteria provided, single submitter clinical testing The E931K variant in the MYH7 gene has been reported in association with HCM in two individuals and was absent from 400 control alleles; however, no additional clinical information or segregation analysis was provided (Van Driest et al., 2004; Berge et al., 2014). The E931K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Variants in nearby residues (E929K, E930Q, E930K, M932K, E935K) have been reported in HGMD in association with HCM (Stenson et al., 2014), further supporting the functional importance of this region of the protein. Furthermore, the E931K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.Therefore, this variant is a strong candidate for a pathogenic variant however the possibility that it is a benign variant cannot be excluded.
Invitae RCV002524033 SCV003270415 pathogenic Hypertrophic cardiomyopathy 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 931 of the MYH7 protein (p.Glu931Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of hypertrophic cardiomyopathy (PMID: 15358028; Invitae). ClinVar contains an entry for this variant (Variation ID: 429657). 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 95%. This variant disrupts the p.Glu931 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been observed in individuals with MYH7-related conditions (PMID: 27574918), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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.