Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001232209 | SCV001404757 | uncertain significance | Renal cell carcinoma | 2019-08-08 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with MET-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 1158 of the MET protein (p.Leu1158Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |
| Ambry Genetics | RCV004033156 | SCV005037888 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-28 | criteria provided, single submitter | clinical testing | The p.L1158F variant (also known as c.3472C>T), located in coding exon 16 of the MET gene, results from a C to T substitution at nucleotide position 3472. The leucine at codon 1158 is replaced by phenylalanine, 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. Based on the available evidence, the clinical significance of this alteration remains unclear. |