ClinVar Miner

Submissions for variant NM_000245.4(MET):c.3392T>C (p.Met1131Thr)

dbSNP: rs121913668
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000565834 SCV000664700 pathogenic Hereditary cancer-predisposing syndrome 2016-11-18 criteria provided, single submitter clinical testing The p.M1149T pathogenic mutation (also known as c.3446T>C), located in coding exon 16 of the MET gene, results from a T to C substitution at nucleotide position 3446. The methionine at codon 1149 is replaced by threonine, an amino acid with similar properties. This alteration has been previously in two families with hereditary papillary renal cell carcinoma, and was shown to segregate with disease (Schmidt L et al. Nat. Genet., 1997 May;16:68-73). Based on structural analysis, this variant is located in the tyrosine kinase domain and is anticipated to perturb normal protein function (Miller M et al. Proteins, 2001 Jul;44:32-43). Functional assays demonstrated that this is a weakly activating mutation resulting in increased phosphorylation (Jeffers M et al. Proc. Natl. Acad. Sci. U.S.A., 1997 Oct;94:11445-50; Schmidt L et al. Oncogene, 1999 Apr;18:2343-50). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV002228027 SCV000944222 pathogenic Renal cell carcinoma 2018-11-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect MET protein function (PMID: 9326629). This variant has been observed to segregate with papillary renal cell carcinoma in two families (PMID: 9140397). ClinVar contains an entry for this variant (Variation ID: 13881). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 1149 of the MET protein (p.Met1149Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine.
OMIM RCV000014895 SCV000035150 pathogenic Papillary renal cell carcinoma type 1 1997-05-01 no assertion criteria provided literature only

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