ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1907T>A (p.Met636Lys)

gnomAD frequency: 0.00001  dbSNP: rs775011117
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002048218 SCV002299085 uncertain significance Renal cell carcinoma 2022-12-09 criteria provided, single submitter clinical testing 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 not expected to disrupt MET protein function. ClinVar contains an entry for this variant (Variation ID: 1514266). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is present in population databases (rs775011117, gnomAD 0.003%). This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 636 of the MET protein (p.Met636Lys). 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 RCV002407303 SCV002720512 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-29 criteria provided, single submitter clinical testing The p.M636K variant (also known as c.1907T>A), located in coding exon 6 of the MET gene, results from a T to A substitution at nucleotide position 1907. The methionine at codon 636 is replaced by lysine, an amino acid with 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.
GeneDx RCV002548791 SCV003194753 uncertain significance not provided 2024-02-16 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.