ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2227A>C (p.Ile743Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002299949 SCV002597141 uncertain significance Renal cell carcinoma 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 743 of the MET protein (p.Ile743Leu). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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).
Ambry Genetics RCV003289507 SCV004008342 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-31 criteria provided, single submitter clinical testing The p.I743L variant (also known as c.2227A>C), located in coding exon 8 of the MET gene, results from an A to C substitution at nucleotide position 2227. The isoleucine at codon 743 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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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