ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2378G>A (p.Arg793Gln) (rs730880896)

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 RCV000158841 SCV000208776 likely pathogenic not provided 2011-07-26 criteria provided, single submitter clinical testing This variant is denoted p.Arg793Gln (R793Q) at the protein level and c.2378 G>A at the cDNA level. The Arg793Gln variant has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. The Arg793Gln results in a non-conservative amino acid substitution of a positively charged Arginine residue with a neutral Glutamine at a position that is highly conserved throughout evolution. In silico analysis predicts Arg793Gln to be damaging to the protein structure/function. Furthermore, mutations in nearby residues (Arg787Cys, Arg787His, Leu796Phe, Ala797Pro, Ala797Thr) have been reported in association with HCM, further supporting the functional importance of this region of the protein. In summary, with the clinical and molecular evidence available at this time, we cannot unequivocally determine the clinical significance of Arg793Gln, athough evidence suggests it is likely disease-causing. The variant is found in HCM panel(s).
Invitae RCV000554316 SCV000623669 uncertain significance Hypertrophic cardiomyopathy 2017-06-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 793 of the MYH7 protein (p.Arg793Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (rs730880896, ExAC no frequency). This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 21750094). ClinVar contains an entry for this variant (Variation ID: 181371). This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.