Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002233335 | SCV000829081 | uncertain significance | Renal cell carcinoma | 2021-05-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with MET-related disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces lysine with arginine at codon 27 of the MET protein (p.Lys27Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. |
| Ambry Genetics | RCV002422562 | SCV002677114 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-22 | criteria provided, single submitter | clinical testing | The p.K27R variant (also known as c.80A>G), located in coding exon 1 of the MET gene, results from an A to G substitution at nucleotide position 80. The lysine at codon 27 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV003332239 | SCV004040344 | uncertain significance | not provided | 2024-05-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |