ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2441C>T (p.Pro814Leu)

gnomAD frequency: 0.00001  dbSNP: rs781452657
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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 RCV000628768 SCV000749674 uncertain significance Renal cell carcinoma 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 832 of the MET protein (p.Pro832Leu). This variant is present in population databases (rs781452657, gnomAD 0.003%). 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: 524888). 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 expected to disrupt MET protein function with a positive 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 RCV001015703 SCV001176566 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-01 criteria provided, single submitter clinical testing The p.P832L variant (also known as c.2495C>T), located in coding exon 10 of the MET gene, results from a C to T substitution at nucleotide position 2495. The proline at codon 832 is replaced by leucine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Sema4, Sema4 RCV001015703 SCV002532127 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-24 criteria provided, single submitter curation
GeneDx RCV004767453 SCV005376337 uncertain significance not provided 2023-10-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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