Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001359622 | SCV001555497 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-06-25 | criteria provided, single submitter | clinical testing | 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 MYH6 protein function. ClinVar contains an entry for this variant (Variation ID: 1051563). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs372300127, gnomAD 0.0008%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 650 of the MYH6 protein (p.Ser650Leu). |
| Gene |
RCV001751700 | SCV001994896 | uncertain significance | not provided | 2023-02-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
| Ambry Genetics | RCV002413847 | SCV002722833 | uncertain significance | Cardiovascular phenotype | 2024-02-25 | criteria provided, single submitter | clinical testing | The p.S650L variant (also known as c.1949C>T), located in coding exon 14 of the MYH6 gene, results from a C to T substitution at nucleotide position 1949. The serine at codon 650 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |