ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1343G>A (p.Gly448Glu)

gnomAD frequency: 0.00002  dbSNP: rs750256779
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000530733 SCV000623374 uncertain significance Renal cell carcinoma 2023-12-26 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 448 of the MET protein (p.Gly448Glu). This variant is present in population databases (rs750256779, 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: 454182). 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 RCV002384026 SCV002693682 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-28 criteria provided, single submitter clinical testing The p.G448E variant (also known as c.1343G>A), located in coding exon 2 of the MET gene, results from a G to A substitution at nucleotide position 1343. The glycine at codon 448 is replaced by glutamic acid, an amino acid with 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003493621 SCV004243307 uncertain significance not specified 2024-02-06 criteria provided, single submitter clinical testing

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