Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CHEO Genetics Diagnostic Laboratory, |
RCV000769458 | SCV000900852 | uncertain significance | Cardiomyopathy | 2017-01-19 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001855981 | SCV002249119 | pathogenic | Hypertrophic cardiomyopathy | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 796 of the MYH7 protein (p.Leu796Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 12974739; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 626545). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002458376 | SCV002738396 | uncertain significance | Cardiovascular phenotype | 2019-08-30 | criteria provided, single submitter | clinical testing | The p.L796F variant (also known as c.2386C>T), located in coding exon 19 of the MYH7 gene, results from a C to T substitution at nucleotide position 2386. The leucine at codon 796 is replaced by phenylalanine, an amino acid with highly similar properties, and is located in the head domain. This variant has been detected in a family with hypertrophic cardiomyopathy; however, clinical details were limited (Erdmann J et al. Clin. Genet., 2003 Oct;64:339-49). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |