Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000429048 | SCV000529849 | uncertain significance | not provided | 2016-07-22 | criteria provided, single submitter | clinical testing | The V1289M variant in the MET gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V1289M variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V1289M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret V1289M as a variant of uncertain significance. |
Labcorp Genetics |
RCV002522386 | SCV000941942 | uncertain significance | Renal cell carcinoma | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1289 of the MET protein (p.Val1289Met). This variant is present in population databases (rs751186512, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 387726). 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 MET protein function with a positive predictive value of 80%. 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 | RCV002356591 | SCV002622861 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-19 | criteria provided, single submitter | clinical testing | The p.V1289M variant (also known as c.3865G>A), located in coding exon 19 of the MET gene, results from a G to A substitution at nucleotide position 3865. The valine at codon 1289 is replaced by methionine, an amino acid with highly similar properties. 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. |
Center for Genomic Medicine, |
RCV003493573 | SCV004243326 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |