ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5380C>G (p.Gln1794Glu) (rs397516247)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035962 SCV000059614 uncertain significance not specified 2018-11-01 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000158697 SCV000208632 likely pathogenic not provided 2012-04-27 criteria provided, single submitter clinical testing p.Gln1794Glu (CAG>GAG): c.5380 C>G in exon 37 of the MYH7 gene (NM_000257.2). The Gln1794Glu variant in the MYH7 gene has not been reported previously as a disease-causing mutation or as a benign variant, to our knowledge. Gln1794Glu results in a semi-conservative amino acid substitution of a neutral, polar Glutamine residue with a negatively charged Glutamic acid residue at a position that is conserved across species throughout evolution. In silico analysis predicts Gln1794Glu is damaging to the structure/function of the protein, and mutations affecting nearby residues (Asp1792Gly, Glu1801Gly) have been reported in association with DCM, supporting the functional importance of this region of the protein. The NHLBI ESP Exome Variant Server reports Gln1794Glu was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Therefore, Gln1794Glu is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in DCM panel(s).
Invitae RCV000471537 SCV000546194 uncertain significance Hypertrophic cardiomyopathy 2016-05-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 1794 of the MYH7 protein (p.Gln1794Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (rs397516247, ExAC no frequency). This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 22464770). ClinVar contains an entry for this variant (Variation ID: 43067). 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770470 SCV000901913 uncertain significance Cardiomyopathy 2017-08-03 criteria provided, single submitter clinical testing

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