ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3551A>T (p.Gln1184Leu) (rs546586969)

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
GeneDx RCV000766447 SCV000208545 uncertain significance not provided 2017-05-26 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH7 gene. The Q1184L variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q1184L 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. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.
Invitae RCV000794278 SCV000933674 uncertain significance Hypertrophic cardiomyopathy 2019-02-04 criteria provided, single submitter clinical testing This sequence change replaces glutamine with leucine at codon 1184 of the MYH7 protein (p.Gln1184Leu). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and leucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MYH7-related disease. ClinVar contains an entry for this variant (Variation ID: 181226). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000223885 SCV000280340 uncertain significance not specified 2014-03-03 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Gln1184Leu in the MYH7 gene at exon 27. This variant is novel and has not been reported as a disease-causing mutation or as a benign polymorphism. This is a non-conserved amino acid substitution which changes an uncharged polar glutamine to a nonpolar leucine residue. In silico analysis with PolyPhen-2 predicts the variant to be possibly damaging with a score of 0.689. Mutation Taster predicts this change to be damaging with a score of 113. The Glutamine at codon 1184 is conserved across species, as are neighboring amino acids. A variant at codon 1193 (p.Arg1193His) has been reported in HGMD in association with cardiomyopathy (Stendon P et al., 2009). In total the variant has not been seen in ~6000 individuals from publicly available population datasets. There is no variation at codon 1184 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6000 Caucasian and African American individuals (as of 5/31/13). Note that this dataset does not match the patient's ancestry. There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 5/31/13).

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.