Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003869503 | SCV004670240 | uncertain significance | Renal cell carcinoma | 2023-07-20 | 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. 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 not expected to disrupt MET protein function. 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 isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 959 of the MET protein (p.Ile959Met). |
Ambry Genetics | RCV004943262 | SCV005447592 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-23 | criteria provided, single submitter | clinical testing | The p.I959M variant (also known as c.2877A>G), located in coding exon 12 of the MET gene, results from an A to G substitution at nucleotide position 2877. The isoleucine at codon 959 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |