Submissions for variant NM_000257.4(MYH7):c.2518C>A (p.Leu840Met) (rs730880747)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158544	SCV000208479	likely pathogenic	not provided	2013-10-28	criteria provided, single submitter	clinical testing	p.Leu840Met (CTG>ATG): c.2518 C>A in exon 22 of the MYH7 gene (NM_000257.2). The Leu840Met variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Leu840Met results in a conservative amino acid substitution of of one non-polar amino acid with another at a position that is conserved across species. In silico analysis predicts Leu840Met is damaging to the protein structure/function. Mutations in nearby residues (Pro838Leu, Glu844Lys, Arg845Gly) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, the Leu840Met 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 Leu840Met 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 HCM panel(s).