Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002234388 | SCV000749659 | uncertain significance | Renal cell carcinoma | 2021-08-12 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MET-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 228 of the MET protein (p.Phe228Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. |
| Ambry Genetics | RCV001025702 | SCV001187945 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-20 | criteria provided, single submitter | clinical testing | The p.F228L variant (also known as c.682T>C), located in coding exon 1 of the MET gene, results from a T to C substitution at nucleotide position 682. The phenylalanine at codon 228 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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. |