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UniProtKB/Swiss-Prot P08581: Variant p.Val1294Ile

Hepatocyte growth factor receptor
Gene: MET
Variant information

Variant position:  1294
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Valine (V) to Isoleucine (I) at position 1294 (V1294I, p.Val1294Ile).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  3
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:  1294
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:   WELMTRGAPPYPDVNTFDIT  V YLLQGRRLLQPEYCPDPLYE
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
Domain 1078 – 1345 Protein kinase
Region 1212 – 1390 Interaction with RANBP9
Modified residue 1289 – 1289 Phosphothreonine
Alternative sequence 765 – 1390 Missing. In isoform 3.
Mutagenesis 1313 – 1313 Y -> F. No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1349, F-1356 and F-1365.
Helix 1292 – 1297


Literature citations

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.