Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010257 | SCV001170426 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-23 | criteria provided, single submitter | clinical testing | The p.K40M variant (also known as c.119A>T), located in coding exon 1 of the MET gene, results from an A to T substitution at nucleotide position 119. The lysine at codon 40 is replaced by methionine, an amino acid with 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. |
| Labcorp Genetics |
RCV001862764 | SCV002192927 | uncertain significance | Renal cell carcinoma | 2022-09-06 | 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. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 818558). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 40 of the MET protein (p.Lys40Met). |
| Gene |
RCV003235445 | SCV003933145 | uncertain significance | not provided | 2022-12-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |