UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1312

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

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Threonine (T) at position 1312 (R1312T, p.Arg1312Thr).

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 basic (R) to medium size and polar (T)

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

BLOSUM score:

-1

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:

In DEE11; modified voltage-gated sodium channel activity; activated with lowered voltage sensitivity; disturbed fast and slow inactivation.

Any additional useful information about the variant.

Sequence information

Variant position:

1312

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

Protein sequence length:

2005

The length of the canonical sequence.

Location on the sequence:

NALGYSELGAIKSLRTLRAL R PLRALSRFEGMRVVVNALLG

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                         NALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLG

Mouse                         NALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLG

Rat                           NALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLG

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 – 2005	Sodium channel protein type 2 subunit alpha
Transmembrane	1301 – 1319	Helical; Name=S4 of repeat III
Repeat	1190 – 1504	III
Helix	1306 – 1316

Literature citations

Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome.
Shi X.; Yasumoto S.; Nakagawa E.; Fukasawa T.; Uchiya S.; Hirose S.;
Brain Dev. 31:758-762(2009)
Cited for: VARIANTS ASN-322 AND VAL-328; VARIANT DEE11 THR-1312;

Prevalence of SCN1A mutations in children with suspected Dravet syndrome and intractable childhood epilepsy.
Wang J.W.; Shi X.Y.; Kurahashi H.; Hwang S.K.; Ishii A.; Higurashi N.; Kaneko S.; Hirose S.;
Epilepsy Res. 102:195-200(2012)
Cited for: VARIANTS LYS-19; ASN-322; VAL-328 AND ASN-649; VARIANT DEE11 THR-1312;

Compromised function in the Na(v)1.2 Dravet syndrome mutation R1312T.
Lossin C.; Shi X.; Rogawski M.A.; Hirose S.;
Neurobiol. Dis. 47:378-384(2012)
Cited for: CHARACTERIZATION OF VARIANT DEE11 THR-1312;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99250: Variant p.Arg1312Thr