UniProtKB/SwissProt variant VAR

Variant information

Variant position:

249

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

Type of variant:

LP/P [Disclaimer]

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 Serine (S) to Cysteine (C) at position 249 (S249C, p.Ser249Cys).

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 small size and polar (S) to medium size and polar (C)

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:

In KERSEB, BLC, cervical cancer and TD1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121913483 [ dbSNP | Ensembl ]

Sequence information

Variant position:

249

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

Protein sequence length:

806

The length of the canonical sequence.

Location on the sequence:

VVENKFGSIRQTYTLDVLER S PHRPILQAGLPANQTAVLGS

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                         VVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGS

Mouse                         VVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAILGS

Chicken                       VVENKYGNIRHTYQLDVLERSPHRPILQAGLPANQTVVVGS

Xenopus laevis                VVENKYGSIRQTYQLDVLERSSHRPILQAGLPGNQTVVLGS

Zebrafish                     VVQNKYGSIKHTYQLDVLERSPHRPILQAGLPANQTVVVGS

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	23 – 806	Fibroblast growth factor receptor 3
Topological domain	23 – 375	Extracellular
Glycosylation	262 – 262	N-linked (GlcNAc...) asparagine

Literature citations

Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.
Tavormina P.L.; Rimoin D.L.; Cohn D.H.; Zhu Y.-Z.; Shiang R.; Wasmuth J.J.;
Hum. Mol. Genet. 4:2175-2177(1995)
Cited for: VARIANT TD1 CYS-249;

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).
Rousseau F.; el Ghouzzi V.; Delezoide A.-L.; Legeai-Mallet L.; le Merrer M.; Munnich A.; Bonaventure J.;
Hum. Mol. Genet. 5:509-512(1996)
Cited for: VARIANTS TD1 CYS-248; CYS-249; CYS-370 AND CYS-373;

Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.
Brodie S.G.; Kitoh H.; Lachman R.S.; Nolasco L.M.; Mekikian P.B.; Wilcox W.R.;
Am. J. Med. Genet. 84:476-480(1999)
Cited for: VARIANTS TD1 CYS-248; CYS-249 AND CYS-373;

Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas.
Cappellen D.; De Oliveira C.; Ricol D.; Gil Diez de Medina S.; Bourdin J.; Sastre-Garau X.; Chopin D.; Thiery J.P.; Radvanyi F.;
Nat. Genet. 23:18-20(1999)
Cited for: VARIANTS BLC CYS-248; CYS-249; CYS-370 AND GLU-650; VARIANTS CERCA CYS-248; CYS-249; CYS-370 AND GLU-650;

Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.
Logie A.; Dunois-Larde C.; Rosty C.; Levrel O.; Blanche M.; Ribeiro A.; Gasc J.-M.; Jorcano J.; Werner S.; Sastre-Garau X.; Thiery J.P.; Radvanyi F.;
Hum. Mol. Genet. 14:1153-1160(2005)
Cited for: VARIANTS KERSEB CYS-248; CYS-249; CYS-370; CYS-371; CYS-373; GLU-650 AND MET-650;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P22607: Variant p.Ser249Cys