ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1354A>G (p.Ile452Val)

dbSNP: rs1793018926
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001045290 SCV001209131 uncertain significance Renal cell carcinoma 2023-08-02 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. 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: 842808). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 452 of the MET protein (p.Ile452Val).
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268416 SCV002550784 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002379523 SCV002691750 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-03 criteria provided, single submitter clinical testing The p.I452V variant (also known as c.1354A>G), located in coding exon 2 of the MET gene, results from an A to G substitution at nucleotide position 1354. The isoleucine at codon 452 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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 this alteration remains unclear.
GeneDx RCV002473176 SCV002769862 uncertain significance not provided 2023-03-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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