ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2076T>G (p.Ile692Met)

gnomAD frequency: 0.00001  dbSNP: rs752740791
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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 RCV001948299 SCV002199760 uncertain significance Renal cell carcinoma 2023-07-19 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MET-related conditions. 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: 1428518). This variant is present in population databases (rs752740791, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 692 of the MET protein (p.Ile692Met).
Ambry Genetics RCV002423077 SCV002727740 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-21 criteria provided, single submitter clinical testing The p.I692M variant (also known as c.2076T>G), located in coding exon 7 of the MET gene, results from a T to G substitution at nucleotide position 2076. The isoleucine at codon 692 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is 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.
GeneDx RCV002473327 SCV002770152 uncertain significance not provided 2022-06-23 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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