ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2081G>A (p.Arg694His) (rs886039030)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000249009 SCV000319723 uncertain significance Cardiovascular phenotype 2015-05-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Well-characterized mutation at same position,Other data supporting pathogenic classification
GeneDx RCV000422742 SCV000513801 likely pathogenic not provided 2018-07-25 criteria provided, single submitter clinical testing The R694H likely pathogenic variant in the MYH7 gene has been reported in association with HCM (Erdmann et al., 2003; Berge et al., 2014; Lopes et al., 2015; Walsh et al., 2017; Jiménez-Jáimez et al., 2017); however, specific clinical information, family history and segregation data were not provided. The R694H variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the R694H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In summary, R694H in the MYH7 gene is interpreted as a likely pathogenic variant.
Invitae RCV000628874 SCV000749782 pathogenic Hypertrophic cardiomyopathy 2018-02-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 694 of the MYH7 protein (p.Arg694His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 12974739, 20819418, 24111713, 27532257, 25351510). ClinVar contains an entry for this variant (Variation ID: 264068). 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). A different missense substitution at this codon (p.Arg694Cys) has been determined to be pathogenic (PMID: 22811549, 23197161, 27247418, 27532257). This suggests that the arginine residue is critical for MYH7 protein function and that other missense substitutions at this position may also be pathogenic. 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.