UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1769

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 Valine (V) to Alanine (A) at position 1769 (V1769A, p.Val1769Ala).

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 hydrophobic (V) to small size and hydrophobic (A)

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, 62 (EIEE62) [MIM:617938]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE62 is characterized by onset of seizures in the first year of life. {ECO:0000269|PubMed:29466837}. 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 EIEE62; prominent gain of channel function, with markedly increased amplitude of the slowly inactivating current component.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1553517274 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1769

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

Protein sequence length:

2000

The length of the canonical sequence.

Location on the sequence:

FFFVSYIIISFLVVVNMYIA V ILENFSVATEESAEPLSEDD

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                         FFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDD

Mouse                         FFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDD

Rat                           FFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDD

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 – 2000	Sodium channel protein type 3 subunit alpha
Transmembrane	1748 – 1770	Helical; Name=S6 of repeat IV
Repeat	1508 – 1806	IV

Literature citations

Mutations in SCN3A cause early infantile epileptic encephalopathy.
Zaman T.; Helbig I.; Bozovic I.B.; DeBrosse S.D.; Bergqvist A.C.; Wallis K.; Medne L.; Maver A.; Peterlin B.; Helbig K.L.; Zhang X.; Goldberg E.M.;
Ann. Neurol. 83:703-717(2018)
Cited for: INVOLVEMENT IN EIEE62; VARIANTS EIEE62 THR-875; LEU-1333; CYS-1642; ALA-1769 AND GLN-1799; CHARACTERIZATION OF VARIANTS EIEE62 THR-875; LEU-1333; CYS-1642; ALA-1769 AND GLN-1799; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NY46: Variant p.Val1769Ala