Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002049896 | SCV002115841 | uncertain significance | Renal cell carcinoma | 2021-08-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 524 of the MET protein (p.Gln524Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MET-related conditions. |
Ambry Genetics | RCV002397767 | SCV002704069 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-04 | criteria provided, single submitter | clinical testing | The p.Q524E variant (also known as c.1570C>G), located in coding exon 4 of the MET gene, results from a C to G substitution at nucleotide position 1570. The glutamine at codon 524 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. 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 |
RCV003320850 | SCV004025690 | uncertain significance | not provided | 2023-02-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |