ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2519T>C (p.Leu840Pro) (rs1131691577)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492999 SCV000582414 likely pathogenic not provided 2015-10-07 criteria provided, single submitter clinical testing The L840P variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It 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. The L840P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties, and this substitution occurs at a position that is conserved across species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. A different missense variant in this same residue (L840M) has been seen in one other individual who had DNA-based testing for HCM at GeneDx. Moreover, multiple missense variants in nearby residues (K835T, P838L, E844K, R845G, E846Q, E846K, K847E, M849T, A850T, A850D) have been reported in the Human Gene Mutation Database in association with HCM (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded

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