Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002027017 | SCV002316785 | uncertain significance | Hypertrophic cardiomyopathy | 2023-08-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1516996). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is present in population databases (rs769054108, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 90 of the MYH7 protein (p.Met90Val). 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. |
| Fulgent Genetics, |
RCV002486736 | SCV002785604 | uncertain significance | Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy | 2021-07-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004641893 | SCV005143061 | uncertain significance | Cardiovascular phenotype | 2024-04-08 | criteria provided, single submitter | clinical testing | The p.M90V variant (also known as c.268A>G), located in coding exon 2 of the MYH7 gene, results from an A to G substitution at nucleotide position 268. The methionine at codon 90 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Harper AR et al. Nat Genet, 2021 Feb;53:135-142). 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 available evidence, the clinical significance of this variant remains unclear. |