Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001067871 | SCV001232953 | uncertain significance | Renal cell carcinoma | 2021-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 1004 of the MET protein (p.Ala1004Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MET-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C25"). 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 | RCV002436670 | SCV002753298 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-07-07 | criteria provided, single submitter | clinical testing | The p.A1004S variant (also known as c.3010G>T), located in coding exon 13 of the MET gene, results from a G to T substitution at nucleotide position 3010. The alanine at codon 1004 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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. |