UniProtKB/SwissProt variant VAR

Variant information

Variant position:

521

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 Tryptophan (W) to Arginine (R) at position 521 (W521R, p.Trp521Arg).

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 aromatic (W) to large size and basic (R)

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:

In LDS2.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1575166666 [ dbSNP | Ensembl ]

Sequence information

Variant position:

521

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

Protein sequence length:

567

The length of the canonical sequence.

Location on the sequence:

PSFWLNHQGIQMVCETLTEC W DHDPEARLTAQCVAERFSEL

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                         PSFWLNHQGIQMVCETLTECWDHDPEARLTAQCVAERFSEL

Mouse                         PSFWLNHQGIQIVCETLTECWDHDPEARLTAQCVAERFSEL

Rat                           PSFWLNHQGIQIVCETLTECWDHDPEARLTAQCVAERFSEL

Chicken                       PSSWLNHQGIQMVCETLIECWDHDPEARLTAQCVAERFSEF

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 – 567	TGF-beta receptor type-2
Topological domain	188 – 567	Cytoplasmic
Domain	244 – 544	Protein kinase
Region	439 – 567	Sufficient for interaction with CLU
Alternative sequence	81 – 567	Missing. In isoform 3.

Literature citations

Germline TGF-beta receptor mutations and skeletal fragility: a report on two patients with Loeys-Dietz syndrome.
Kirmani S.; Tebben P.J.; Lteif A.N.; Gordon D.; Clarke B.L.; Hefferan T.E.; Yaszemski M.J.; McGrann P.S.; Lindor N.M.; Ellison J.W.;
Am. J. Med. Genet. A 152:1016-1019(2010)
Cited for: VARIANTS LDS2 PRO-308 AND ARG-521;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P37173: Variant p.Trp521Arg