Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001246915 | SCV001420307 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 6 of the MYH7 protein (p.Met6Thr). This variant is present in population databases (rs779276614, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 971190). 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 with a positive predictive value of 95%. 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. |
| Gene |
RCV001788432 | SCV002031042 | uncertain significance | not provided | 2021-06-04 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27387980, 27535533) |
| Ambry Genetics | RCV002411908 | SCV002715026 | uncertain significance | Cardiovascular phenotype | 2022-08-11 | criteria provided, single submitter | clinical testing | The p.M6T variant (also known as c.17T>C), located in coding exon 1 of the MYH7 gene, results from a T to C substitution at nucleotide position 17. The methionine at codon 6 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |