UniProtKB/Swiss-Prot P08581: Variant p.Thr992Ile

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 992 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: US 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; uncertain significance; somatic mutation; the mutated receptor is still functional and can sustain the transformed phenotype. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs56391007 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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;