UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1256

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 Arginine (R) to Serine (S) at position 1256 (R1256S, p.Arg1256Ser).

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 small size and polar (S)

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 IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts.

Any additional useful information about the variant.

Sequence information

Variant position:

1256

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

Protein sequence length:

1367

The length of the canonical sequence.

Location on the sequence:

NCPDMLFELMRMCWQYNPKM R PSFLEIISSIKEEMEPGFRE

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                         NCPDMLFELMRMCWQYNPKMRPSFLEIISSIKEEMEPGFRE

Mouse                         NCPDMLFELMRMCWQYNPKMRPSFLEIIGSIKDEMEPSFQE

Rat                           NCPDMLFELMRMCWQYNPKMRPSFLEIIGSIKDEMEPSFQE

Xenopus laevis                NCPDMLFELMRMCWQFNPKMRPSFLEIISSIKDELDPGFKE

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	741 – 1367	Insulin-like growth factor 1 receptor beta chain
Topological domain	960 – 1367	Cytoplasmic
Domain	999 – 1274	Protein kinase

Literature citations

Three novel IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment.
Juanes M.; Guercio G.; Marino R.; Berensztein E.; Warman D.M.; Ciaccio M.; Gil S.; Bailez M.; Rivarola M.A.; Belgorosky A.;
Clin. Endocrinol. (Oxf.) 82:704-711(2015)
Cited for: VARIANTS IGF1RES TYR-359; CYS-865; SER-1256 AND CYS-1337; CHARACTERIZATION OF VARIANTS IGF1RES TYR-359; CYS-865; SER-1256 AND CYS-1337;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08069: Variant p.Arg1256Ser