Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002235585 | SCV000965242 | uncertain significance | Renal cell carcinoma | 2021-03-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 483 of the MET protein (p.Ser483Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant has not been reported in the literature in individuals with MET-related disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV002390715 | SCV002701554 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-20 | criteria provided, single submitter | clinical testing | The p.S483P variant (also known as c.1447T>C), located in coding exon 3 of the MET gene, results from a T to C substitution at nucleotide position 1447. The serine at codon 483 is replaced by proline, 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. |