ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2222G>A (p.Gly741Glu) (rs1057520814)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000429053 SCV000518150 likely pathogenic not provided 2016-12-29 criteria provided, single submitter clinical testing A variant that is likely pathogenic was identified in the MYH7 gene. The G741E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G741E 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. G741E 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 where only amino acids with similar properties to Glycine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, different pathogenic missense variants at the same residues (G741R, G741W) have been reported in the Human Gene Mutation Database and at GeneDx in association with HCM (Stenson et al., 2014), supporting the functional importance of this residue. However, to our knowledge no studies have been performed to determine the functional effect of the G741E variant.Therefore, this variant is likely pathogenic. In order to definitively determine its clinical significance, additional data is required.

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