UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1451

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 Glycine (G) to Serine (S) at position 1451 (G1451S, p.Gly1451Ser).

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 glycine (G) to small size and polar (S)

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:

Epileptic encephalopathy, early infantile, 13 (EIEE13) [MIM:614558]: A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. EIEE13 is a severe form consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy. {ECO:0000269|PubMed:22365152, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:24352161, ECO:0000269|PubMed:24874546, ECO:0000269|PubMed:24888894, ECO:0000269|PubMed:25239001, ECO:0000269|PubMed:25568300, ECO:0000269|PubMed:25725044, ECO:0000269|PubMed:25785782, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26900580, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27210545, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28923014}. 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 EIEE13; loss of channel activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs863223345 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1451

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

Protein sequence length:

1980

The length of the canonical sequence.

Location on the sequence:

QPKYEDNIYMYIYFVIFIIF G SFFTLNLFIGVIIDNFNQQK

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                         QPKYEDNIYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQK

Mouse                         QPDYEGNIYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQK

Rat                           QPDYEGNIYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQK

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 – 1980	Sodium channel protein type 8 subunit alpha
Transmembrane	1439 – 1460	Helical; Name=S6 of repeat III
Repeat	1180 – 1495	III
Alternative sequence	1284 – 1980	Missing. In isoform 4.

Literature citations

De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.
Blanchard M.G.; Willemsen M.H.; Walker J.B.; Dib-Hajj S.D.; Waxman S.G.; Jongmans M.C.; Kleefstra T.; van de Warrenburg B.P.; Praamstra P.; Nicolai J.; Yntema H.G.; Bindels R.J.; Meisler M.H.; Kamsteeg E.J.;
J. Med. Genet. 52:330-337(2015)
Cited for: VARIANTS EIEE13 ASN-58; LYS-984 AND SER-1451; CHARACTERIZATION OF VARIANTS EIEE13 ASN-58; LYS-984 AND SER-1451;

UniProtKB/Swiss-Prot Q9UQD0: Variant p.Gly1451Ser