UniProtKB/Swiss-Prot P08581: Variant p.Val1294Ile

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 1294 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 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; 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 rs1263785859 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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;