Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001215169 | SCV001386899 | uncertain significance | Renal cell carcinoma | 2023-02-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 944707). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 595 of the MET protein (p.Lys595Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MET-related conditions. 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. 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. |
Ambry Genetics | RCV002411792 | SCV002714964 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-23 | criteria provided, single submitter | clinical testing | The p.K595T variant (also known as c.1784A>C), located in coding exon 5 of the MET gene, results from an A to C substitution at nucleotide position 1784. The lysine at codon 595 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |