ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2707G>A (p.Glu903Lys) (rs730880756)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics,University of Leuven RCV000768487 SCV000886791 likely pathogenic Hypertrophic cardiomyopathy 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000768487 SCV000948076 uncertain significance Hypertrophic cardiomyopathy 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 903 of the MYH7 protein (p.Glu903Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 20031618). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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). 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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