UniProtKB/SwissProt variant VAR

Variant information

Variant position:

121

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 Cysteine (C) to Tryptophan (W) at position 121 (C121W, p.Cys121Trp).

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 (C) to large size and aromatic (W)

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

Involvement in disease:

Generalized epilepsy with febrile seizures plus 1 (GEFS+1) [MIM:604233]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. {ECO:0000269|PubMed:17928445, ECO:0000269|PubMed:21040232, ECO:0000269|PubMed:9697698}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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 GEFS+1; can rescue the loss of function and defective trafficking to cell membrane phenotype of the SCN1A variant Thr-1852.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894718 [ dbSNP | Ensembl ]

Sequence information

Variant position:

121

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

Protein sequence length:

218

The length of the canonical sequence.

Location on the sequence:

LQDLSIFITNVTYNHSGDYE C HVYRLLFFENYEHNTSVVKK

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                         LQDLSIFITNVTYNHSGDYECHVYRLLFFENYEHNTSVVKK

                              LQDLSIFITNVTYNHSGDYECHVYRLLFFENYEHNTSVVKK

Chimpanzee                    LQDLSIFITNVTYNHSGDYECHVYRLLFFENYEHNTSVVKK

Mouse                         LQDLSIFITNVTYNHSGDYECHVYRLLFFDNYEHNTSVVKK

Rat                           LQDLSIFITNVTYNHSGDYECHVYRLLFFDNYEHNTSVVKK

Bovine                        LQDLSIFITNVTYNHSGDYECHVYRLLFFDNYEHNTSVVKK

Rabbit                        LQDLSIFITNVTYNHSGDYQCHVYRLLSFENYEHNTSVVKK

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	19 – 218	Sodium channel subunit beta-1
Topological domain	19 – 160	Extracellular
Domain	22 – 150	Ig-like C2-type
Glycosylation	110 – 110	N-linked (GlcNAc...) asparagine
Glycosylation	114 – 114	N-linked (GlcNAc...) asparagine
Glycosylation	135 – 135	N-linked (GlcNAc...) asparagine
Disulfide bond	40 – 121
Beta strand	117 – 123

Literature citations

Febrile seizures and generalized epilepsy associated with a mutation in the Na(+)-channel beta-1 subunit gene SCN1B.
Wallace R.H.; Wang D.W.; Singh R.; Scheffer I.E.; George A.L. Jr.; Phillips H.A.; Saar K.; Reis A.; Johnson E.W.; Sutherland G.R.; Berkovic S.F.; Mulley J.C.;
Nat. Genet. 19:366-370(1998)
Cited for: VARIANT GEFS+1 TRP-121;

Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 Na+ channel mutant.
Rusconi R.; Scalmani P.; Cassulini R.R.; Giunti G.; Gambardella A.; Franceschetti S.; Annesi G.; Wanke E.; Mantegazza M.;
J. Neurosci. 27:11037-11046(2007)
Cited for: CHARACTERIZATION OF VARIANT GEFS+1 TRP-121; INTERACTION WITH SCN1A; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q07699: Variant p.Cys121Trp