ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5530G>A (p.Glu1844Lys) (rs730880821)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158706 SCV000208641 likely pathogenic not provided 2014-12-29 criteria provided, single submitter clinical testing The Glu1844Lys variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Glu1844Lys results in a non-conservative amino acid substitution of a negatively charged Glutamic acid with a positively charged Lysine at a position that is conserved across species. In silico analysis predicts Glu1844Lys is damaging to the protein structure/function. Mutations in nearby residues (Ser1836Leu, Arg1845Trp, Arg1846Cys, Thr1854Met) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, the Glu1844Lys 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. In summary, while Glu1844Lys is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in DCM panel(s).
Invitae RCV000469554 SCV000546202 uncertain significance Hypertrophic cardiomyopathy 2018-08-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1844 of the MYH7 protein (p.Glu1844Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs730880821, ExAC 0.002%). This variant has been observed in several individuals affected with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 181285). 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: "Probably Damaging"; 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.

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