Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000599626 | SCV000199262 | likely pathogenic | Hypertrophic cardiomyopathy | 2016-12-02 | criteria provided, single submitter | clinical testing | The p.Phe247Leu variant in MYH7 has been reported in 5 individuals with HCM and segregated with disease in 5 affected relatives from 2 families, including 2 aff ected obligate carriers (Garcia-Castro 2009, Coto 2012, LMM data). This variant was absent from large population studies. Phenylalanine (Phe) at position 247 is highly conserved in mammals and across evolutionarily distant species and the c hange to leucine (Leu) was predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogenic prediction is es timated to be correct 94% of the time (Jordan 2011). In summary, although additi onal studies are required to fully establish its clinical significance, the p.Ph e247Leu variant is likely pathogenic. |
| Ambry Genetics | RCV002381471 | SCV002673961 | likely pathogenic | Cardiovascular phenotype | 2022-02-18 | criteria provided, single submitter | clinical testing | The p.F247L variant (also known as c.739T>C), located in coding exon 7 of the MYH7 gene, results from a T to C substitution at nucleotide position 739. The phenylalanine at codon 247 is replaced by leucine, an amino acid with highly similar properties. This 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 (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). Additional segregation with disease has been reported in a family with HCM who had testing performed at outside laboratories (personal communication). In addition, this variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |