UniProtKB/SwissProt variant VAR

Variant information

Variant position:

691

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 Alanine (A) to Threonine (T) at position 691 (A691T, p.Ala691Thr).

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 polar (T)

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

BLOSUM score:

0

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

Involvement in disease:

Hydrocephalus due to stenosis of the aqueduct of Sylvius (HSAS) [MIM:307000]: Hydrocephalus is a condition in which abnormal accumulation of cerebrospinal fluid in the brain causes increased intracranial pressure inside the skull. This is usually due to blockage of cerebrospinal fluid outflow in the brain ventricles or in the subarachnoid space at the base of the brain. In children is typically characterized by enlargement of the head, prominence of the forehead, brain atrophy, mental deterioration, and convulsions. In adults the syndrome includes incontinence, imbalance, and dementia. HSAS is characterized by mental retardation and enlarged brain ventricles. {ECO:0000269|PubMed:10797421, ECO:0000269|PubMed:11857550, ECO:0000269|PubMed:12435569, ECO:0000269|PubMed:12514225, ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:20621658, ECO:0000269|PubMed:22344793, ECO:0000269|PubMed:22973895, ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:7562969, ECO:0000269|PubMed:7762552, ECO:0000269|PubMed:7881431, ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:8401576, ECO:0000269|PubMed:8556302, ECO:0000269|PubMed:8929944, ECO:0000269|PubMed:9118141, ECO:0000269|PubMed:9195224, ECO:0000269|PubMed:9268105, ECO:0000269|PubMed:9521424, ECO:0000269|PubMed:9744477, ECO:0000269|PubMed:9832035}. Note=The disease is caused by mutations affecting the gene represented in this entry. L1CAM mutations have also been found in few patients affected by hydrocephalus with Hirschsprung disease, suggesting a role of this gene acting either in a direct or indirect way in the pathogenesis of Hirschsprung disease (PubMed:22344793). {ECO:0000269|PubMed:22344793}.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In HSAS.

Any additional useful information about the variant.

Sequence information

Variant position:

691

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:

NQTSTTLKLSPYVHYTFRVT A INKYGPGEPSPVSETVVTPE

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                         NQTSTTLKLSPYVHYTFRVTAINKYGPGEPSPVSETVVTPE

Mouse                         NQTSTTLKLSPYVHYTFRVTAINKYGPGEPSPVSESVVTPE

Rat                           NQTSTTLKLSPYVHYTFRVTAINKYGPGEPSPVSETVVTPE

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
Glycosylation	671 – 671	N-linked (GlcNAc...) asparagine

Literature citations

Spectrum and detection rate of L1CAM mutations in isolated and familial cases with clinically suspected L1-disease.
Finckh U.; Schroeder J.; Ressler B.; Veske A.; Gal A.;
Am. J. Med. Genet. 92:40-46(2000)
Cited for: VARIANTS HSAS TRP-184; CYS-335; ILE-408; ASP-421; TYR-497; THR-691 AND PRO-751; VARIANTS ASN-30; TRP-739 AND GLU-1239; VARIANT HSAS/MASA ARG-370;

UniProtKB/Swiss-Prot P32004: Variant p.Ala691Thr