ClinVar

Description

The p.F247L variant (also known as c.741C>A), located in coding exon 7 of the MYH7 gene, results from a C to A substitution at nucleotide position 741. The phenylalanine at codon 247 is replaced by leucine, an amino acid with highly similar properties. The p.F247L variant was detected in an individual with hypertrophic cardiomyopathy (HCM) and his affected relative, as well as reported in individuals from HCM cohorts with limited clinical information provided; some of these reports were documented to have an alternate nucleotide change, c.739T>C, while others did not list the specific nucleotide change associated (García-Castro M et al. Rev Esp Cardiol, 2009 Jan;62:48-56; Coto E et al. J Mol Diagn, 2012 Sep;14:518-24; Walsh R et al. Genet. Med., 2017 02;19:192-203). In addition, the c.739T>C variant has been reported to segregate with disease in a family with HCM that had testing performed at outside laboratories (personal communication). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.