ClinVar Miner

Submissions for variant NM_000245.4(MET):c.994C>A (p.Gln332Lys)

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
Ambry Genetics RCV002382907 SCV002694380 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-10 criteria provided, single submitter clinical testing The p.Q332K variant (also known as c.994C>A), located in coding exon 1 of the MET gene, results from a C to A substitution at nucleotide position 994. The glutamine at codon 332 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6020 samples (12040 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 4500 alleles tested) in our clinical cohort. This amino acid position is 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 p.Q332K remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003774224 SCV004620260 uncertain significance Renal cell carcinoma 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 332 of the MET protein (p.Gln332Lys). This variant is not present in population databases (gnomAD no frequency). 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: 1768690). 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. 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.

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.