ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2265-49G>C

dbSNP: rs1196543273
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001753301 SCV002007299 uncertain significance not provided 2021-03-19 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); 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 RCV001868729 SCV002159010 uncertain significance Renal cell carcinoma 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 757 of the MET protein (p.Trp757Ser). This variant is not present in population databases (gnomAD no frequency). 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: 1318526). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV004040732 SCV005037915 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-23 criteria provided, single submitter clinical testing The p.W757S variant (also known as c.2270G>C), located in coding exon 9 of the MET gene, results from a G to C substitution at nucleotide position 2270. The tryptophan at codon 757 is replaced by serine, an amino acid with highly dissimilar 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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