UniProtKB/Swiss-Prot P07949: Variant p.Arg749Thr

Proto-oncogene tyrosine-protein kinase receptor Ret
Gene: RET
Feedback?

Variant information Variant position:

749 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 Arginine (R) to Threonine (T) at position 749 (R749T, p.Arg749Thr). 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 large size and basic (R) to medium size and polar (T) 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
Other resources:

Links to websites of interest for the variant.

Variant rs34288963 [ dbSNP | Ensembl ]

Sequence information Variant position:

749 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1114 The length of the canonical sequence.
Location on the sequence:

TLGEGEFGKVVKATAFHLKG R AGYTTVAVKMLKENASPSEL 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.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         TLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSEL

Mouse                         TLGEGEFGKVVKATAFRLKGRAGYTTVAVKMLKENASQSEL

Rat                           TLGEGEFGKVVKATAFRLKGRAGYTTVAVKMLKENASQSEL

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	29 – 1114	Proto-oncogene tyrosine-protein kinase receptor Ret
Chain	708 – 1017	Soluble RET kinase fragment
Topological domain	658 – 1114	Cytoplasmic
Domain	724 – 1016	Protein kinase
Binding site	758 – 758
Mutagenesis	708 – 1114	Missing. Loss of induced cell death, but increased cell aggregation.
Mutagenesis	734 – 734	E -> A. Enhanced protein autophosphorylation due to enhanced substrate presentation in trans.
Mutagenesis	758 – 758	K -> RM. Loss of kinase activity. No effect on interaction with and dissociation from CBLC and CD2AP.

Literature citations
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-163; ASN-278; MET-292; ASN-489; SER-691; THR-749; SER-826; LEU-844; CYS-982 AND TYR-1112;

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.