UniProtKB/SwissProt variant VAR

Variant information

Variant position:

635

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Tryptophan (W) to Cysteine (C) at position 635 (W635C, p.Trp635Cys).

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 medium size and polar (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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:

Probable disease-associated mutation found in L1 syndrome; loss of localization at the cell surface; retention in the endoplasmic reticulum; loss of transport into axons; loss of neurite outgrowth; loss of cell-cell adhesion.

Any additional useful information about the variant.

Sequence information

Variant position:

635

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

Protein sequence length:

1257

The length of the canonical sequence.

Location on the sequence:

VPRLVLSDLHLLTQSQVRVS W SPAEDHNAPIEKYDIEFEDK

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                         VPRLVLSDLHLLTQSQVRVSWSPAEDHNAPIEKYDIEFEDK

Mouse                         VPHLELSDRHLLKQSQVHLSWSPAEDHNSPIEKYDIEFEDK

Rat                           VPHLELSDRHLLKQSQVHLSWSPAEDHNSPIEKYDIEFEDK

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	20 – 1257	Neural cell adhesion molecule L1
Topological domain	20 – 1120	Extracellular
Domain	615 – 712	Fibronectin type-III 1

Literature citations

Pathomechanistic characterization of two exonic L1CAM variants located in trans in an obligate carrier of X-linked hydrocephalus.
Marx M.; Diestel S.; Bozon M.; Keglowich L.; Drouot N.; Bouche E.; Frebourg T.; Minz M.; Saugier-Veber P.; Castellani V.; Schaefer M.K.;
Neurogenetics 13:49-59(2012)
Cited for: INVOLVEMENT IN L1 SYNDROME; VARIANTS CYS-635 AND ILE-768; GLYCOSYLATION;

UniProtKB/Swiss-Prot P32004: Variant p.Trp635Cys