Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003182872 | SCV003869881 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-06 | criteria provided, single submitter | clinical testing | The p.A1224S variant (also known as c.3670G>T), located in coding exon 17 of the MET gene, results from a G to T substitution at nucleotide position 3670. The alanine at codon 1224 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003761636 | SCV004431894 | uncertain significance | Renal cell carcinoma | 2023-01-23 | 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 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 alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1224 of the MET protein (p.Ala1224Ser). |