ClinVar Miner

Submissions for variant NM_000245.4(MET):c.173A>G (p.His58Arg)

gnomAD frequency: 0.00001  dbSNP: rs374578653
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002235388 SCV000960189 uncertain significance Renal cell carcinoma 2023-09-19 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 58 of the MET protein (p.His58Arg). This variant is present in population databases (rs374578653, gnomAD 0.004%). 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: 661993). 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.
GeneDx RCV001776037 SCV002012788 uncertain significance not provided 2022-01-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002397713 SCV002710235 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-06 criteria provided, single submitter clinical testing The p.H58R variant (also known as c.173A>G), located in coding exon 1 of the MET gene, results from an A to G substitution at nucleotide position 173. The histidine at codon 58 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved through mammals. 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.
Breakthrough Genomics, Breakthrough Genomics RCV001776037 SCV005195603 uncertain significance not provided criteria provided, single submitter not provided

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.