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UniProtKB/Swiss-Prot P08581: Variant p.Thr992Ile

Hepatocyte growth factor receptor
Gene: MET
Variant information

Variant position:  992
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LB/B
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Threonine (T) to Isoleucine (I) at position 992 (T992I, p.Thr992Ile).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (T) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  992
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1390
The length of the canonical sequence.

Location on the sequence:   DARVHTPHLDRLVSARSVSP  T TEMVSNESVDYRATFPEDQF
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 25 – 1390 Hepatocyte growth factor receptor
Topological domain 956 – 1390 Cytoplasmic
Site 1003 – 1003 Required for ligand-induced CBL-mediated ubiquitination
Modified residue 977 – 977 Phosphothreonine
Modified residue 990 – 990 Phosphoserine
Modified residue 997 – 997 Phosphoserine
Modified residue 1000 – 1000 Phosphoserine
Modified residue 1003 – 1003 Phosphotyrosine
Alternative sequence 765 – 1390 Missing. In isoform 3.


Literature citations

A novel germ line juxtamembrane Met mutation in human gastric cancer.
Lee J.-H.; Han S.-U.; Cho H.; Jennings B.; Gerrard B.; Dean M.; Schmidt L.; Zbar B.; Vande Woude G.F.V.;
Oncogene 19:4947-4953(2000)
Cited for: VARIANT GASTRIC CANCER SER-991; VARIANT ILE-992; CHARACTERIZATION OF VARIANT GASTRIC CANCER SER-991; CHARACTERIZATION OF VARIANT ILE-992;

A genetic variant that disrupts MET transcription is associated with autism.
Campbell D.B.; Sutcliffe J.S.; Ebert P.J.; Militerni R.; Bravaccio C.; Trillo S.; Elia M.; Schneider C.; Melmed R.; Sacco R.; Persico A.M.; Levitt P.;
Proc. Natl. Acad. Sci. U.S.A. 103:16834-16839(2006)
Cited for: POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO AUTS9; VARIANTS CYS-970 AND ILE-992;

Patterns of somatic mutation in human cancer genomes.
Greenman C.; Stephens P.; Smith R.; Dalgliesh G.L.; Hunter C.; Bignell G.; Davies H.; Teague J.; Butler A.; Stevens C.; Edkins S.; O'Meara S.; Vastrik I.; Schmidt E.E.; Avis T.; Barthorpe S.; Bhamra G.; Buck G.; Choudhury B.; Clements J.; Cole J.; Dicks E.; Forbes S.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jenkinson A.; Jones D.; Menzies A.; Mironenko T.; Perry J.; Raine K.; Richardson D.; Shepherd R.; Small A.; Tofts C.; Varian J.; Webb T.; West S.; Widaa S.; Yates A.; Cahill D.P.; Louis D.N.; Goldstraw P.; Nicholson A.G.; Brasseur F.; Looijenga L.; Weber B.L.; Chiew Y.-E.; DeFazio A.; Greaves M.F.; Green A.R.; Campbell P.; Birney E.; Easton D.F.; Chenevix-Trench G.; Tan M.-H.; Khoo S.K.; Teh B.T.; Yuen S.T.; Leung S.Y.; Wooster R.; Futreal P.A.; Stratton M.R.;
Nature 446:153-158(2007)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-143; LEU-156; ASP-168; SER-375; CYS-970 AND ILE-992;

MET mutations in cancers of unknown primary origin (CUPs).
Stella G.M.; Benvenuti S.; Gramaglia D.; Scarpa A.; Tomezzoli A.; Cassoni P.; Senetta R.; Venesio T.; Pozzi E.; Bardelli A.; Comoglio P.M.;
Hum. Mutat. 32:44-50(2011)
Cited for: VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294; CHARACTERIZATION OF VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294; POSSIBLE INVOLVEMENT IN CUP;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.