UniProtKB/SwissProt variant VAR

Variant information

Variant position:

242

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 Threonine (T) to Isoleucine (I) at position 242 (T242I, p.Thr242Ile).

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 medium size and polar (T) to medium size and hydrophobic (I)

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 AHO.

Any additional useful information about the variant.

Sequence information

Variant position:

242

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

Protein sequence length:

394

The length of the canonical sequence.

Location on the sequence:

FDVGGQRDERRKWIQCFNDV T AIIFVVASSSYNMVIREDNQ

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                         FDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQ

Mouse                         FDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQ

Rat                           FDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQ

Bovine                        FDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQ

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	2 – 394	Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Domain	39 – 394	G-alpha
Mutagenesis	227 – 227	Q -> L. Increases binding to GAS2L2; when associated with N-295.
Mutagenesis	258 – 258	R -> A. Increases GDP release and impairs receptor-mediated activation; markedly elevated intrinsic GTPase rate which will lead to more rapid inactivation.

Literature citations

Analysis of GNAS1 and overlapping transcripts identifies the parental origin of mutations in patients with sporadic Albright hereditary osteodystrophy and reveals a model system in which to observe the effects of splicing mutations on translated and untranslated messenger RNA.
Rickard S.J.; Wilson L.C.;
Am. J. Hum. Genet. 72:961-974(2003)
Cited for: VARIANTS AHO ILE-242; SER-246 AND VAL-259;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P63092: Variant p.Thr242Ile