Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021364 | SCV001182972 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-08 | criteria provided, single submitter | clinical testing | The p.L130F variant (also known as c.388C>T), located in coding exon 1 of the MET gene, results from a C to T substitution at nucleotide position 388. The leucine at codon 130 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003769541 | SCV004635245 | uncertain significance | Renal cell carcinoma | 2023-03-27 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 130 of the MET protein (p.Leu130Phe). ClinVar contains an entry for this variant (Variation ID: 824341). 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. 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. |