ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2265-10G>T

dbSNP: rs1355716761
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 RCV001247152 SCV001420559 uncertain significance Renal cell carcinoma 2021-08-02 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine 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. This variant has not been reported in the literature in individuals with MET-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with phenylalanine at codon 770 of the MET protein (p.Cys770Phe). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and phenylalanine.
Ambry Genetics RCV003166554 SCV003911227 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-06 criteria provided, single submitter clinical testing The p.C770F variant (also known as c.2309G>T), located in coding exon 9 of the MET gene, results from a G to T substitution at nucleotide position 2309. The cysteine at codon 770 is replaced by phenylalanine, an amino acid with highly dissimilar 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.

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.