UniProtKB/SwissProt variant VAR

Variant information

Variant position:

665

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 Alanine (A) to Proline (P) at position 665 (A665P, p.Ala665Pro).

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 hydrophobic (A) to medium size and hydrophobic (P)

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 rs2071240 [ dbSNP | Ensembl ]

Sequence information

Variant position:

665

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

Protein sequence length:

1488

The length of the canonical sequence.

Location on the sequence:

PKKTNTTASAKVAPVRVGTQ A PRKAGTATSPAGSSPAVAGG

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                         PKKTNTTASAKVAPVRVGTQAPRKAGTATSPAG-SSPAVAGG

Mouse                         SRKGTPASATGAS-----TSSHCKAGAVTSSASLSSPALAK

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	1 – 1488	Treacle protein
Region	57 – 1288	Disordered
Modified residue	679 – 679	Phosphoserine

Literature citations

Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome.
Dixon J.; Edwards S.J.; Gladwin A.J.; Dixon M.J.; Loftus S.K.; Bonner C.A.; Koprivnikar K.; Wasmuth J.J.;
Nat. Genet. 12:130-136(1996)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); VARIANTS PRO-665 AND ALA-887;

Identification of the complete coding sequence and genomic organization of the Treacher Collins syndrome gene.
Dixon J.; Edwards S.J.; Anderson I.; Brass A.; Scambler P.J.; Dixon M.J.;
Genome Res. 7:223-234(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2); VARIANTS PRO-665 AND ALA-887;

TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins syndrome throughout its coding region.
Wise C.A.; Chiang L.C.; Paznekas W.A.; Sharma M.; Musy M.M.; Ashley J.A.; Lovett M.; Jabs E.W.;
Proc. Natl. Acad. Sci. U.S.A. 94:3110-3115(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]; VARIANTS PRO-665 AND ALA-887;

Another face of the Treacher Collins syndrome (TCOF1) gene: identification of additional exons.
So R.B.; Gonzales B.; Henning D.; Dixon J.; Dixon M.J.; Valdez B.C.;
Gene 328:49-57(2004)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); ALTERNATIVE SPLICING (ISOFORM 4); VARIANTS PRO-665 AND ALA-887;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13428: Variant p.Ala665Pro