ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2464A>G (p.Met822Val)

dbSNP: rs368787826
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000819875 SCV000960560 uncertain significance Renal cell carcinoma 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 840 of the MET protein (p.Met840Val). This variant is present in population databases (rs368787826, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 662263). 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 with a negative predictive value of 80%. 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 RCV002427046 SCV002744377 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-03 criteria provided, single submitter clinical testing The p.M840V variant (also known as c.2518A>G), located in coding exon 10 of the MET gene, results from an A to G substitution at nucleotide position 2518. The methionine at codon 840 is replaced by valine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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.