Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002048218 | SCV002299085 | uncertain significance | Renal cell carcinoma | 2022-12-09 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt MET protein function. ClinVar contains an entry for this variant (Variation ID: 1514266). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is present in population databases (rs775011117, gnomAD 0.003%). This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 636 of the MET protein (p.Met636Lys). 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. |
Ambry Genetics | RCV002407303 | SCV002720512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-29 | criteria provided, single submitter | clinical testing | The p.M636K variant (also known as c.1907T>A), located in coding exon 6 of the MET gene, results from a T to A substitution at nucleotide position 1907. The methionine at codon 636 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV002548791 | SCV003194753 | uncertain significance | not provided | 2024-02-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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 |