ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2435A>C (p.Gln812Pro)

gnomAD frequency: 0.00001  dbSNP: rs777833095
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001776325 SCV002012800 uncertain significance not provided 2023-09-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001868801 SCV002176903 uncertain significance Renal cell carcinoma 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 830 of the MET protein (p.Gln830Pro). This variant is present in population databases (rs777833095, gnomAD 0.007%). 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: 1320346). 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 RCV004040772 SCV005037936 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-05 criteria provided, single submitter clinical testing The p.Q830P variant (also known as c.2489A>C), located in coding exon 10 of the MET gene, results from an A to C substitution at nucleotide position 2489. The glutamine at codon 830 is replaced by proline, an amino acid with similar properties. This amino acid position is not 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 this alteration remains unclear.

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