Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV000208036 | SCV000264080 | uncertain significance | Left ventricular noncompaction cardiomyopathy | 2015-08-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001323678 | SCV001514602 | uncertain significance | Hypertrophic cardiomyopathy | 2023-03-08 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 466 of the MYH7 protein (p.Glu466Lys). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. ClinVar contains an entry for this variant (Variation ID: 222722). |
| Gene |
RCV001555393 | SCV001776805 | uncertain significance | not provided | 2019-11-01 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002390559 | SCV002697131 | uncertain significance | Cardiovascular phenotype | 2022-08-26 | criteria provided, single submitter | clinical testing | The p.E466K variant (also known as c.1396G>A), located in coding exon 12 of the MYH7 gene, results from a G to A substitution at nucleotide position 1396. The glutamic acid at codon 466 is replaced by lysine, an amino acid with similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). 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. |