UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1872

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 Glutamine (Q) at position 1872 (R1872Q, p.Arg1872Gln).

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 (Q)

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 DEE13; gain-of-function mutation; increased channel activity; impaired channel inactivation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs796053229 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1872

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:

TKRVLGDSGELDILRQQMEE R FVASNPSKVSYEPITTTLRR

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                         TKRVLGDSGELDILRQQMEERFVASNPSKVSYEPITTTLRR

Mouse                         TKRVLGDSGELDILRQQMEERFVASNPSKVSYEPITTTLRR

Rat                           TKRVLGDSGELDILRQQMEERFVASNPSKVSYEPITTTLRR

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
Topological domain	1766 – 1980	Cytoplasmic
Alternative sequence	1284 – 1980	Missing. In isoform 4.

Literature citations

The phenotypic spectrum of SCN8A encephalopathy.
Larsen J.; Carvill G.L.; Gardella E.; Kluger G.; Schmiedel G.; Barisic N.; Depienne C.; Brilstra E.; Mang Y.; Nielsen J.E.; Kirkpatrick M.; Goudie D.; Goldman R.; Jaehn J.A.; Jepsen B.; Gill D.; Doecker M.; Biskup S.; McMahon J.M.; Koeleman B.; Harris M.; Braun K.; de Kovel C.G.; Marini C.; Specchio N.; Djemie T.; Weckhuysen S.; Tommerup N.; Troncoso M.; Troncoso L.; Bevot A.; Wolff M.; Hjalgrim H.; Guerrini R.; Scheffer I.E.; Mefford H.C.; Moeller R.S.;
Neurology 84:480-489(2015)
Cited for: VARIANTS DEE13 ARG-215; SER-260; LEU-410; VAL-479; THR-890; ASP-960; VAL-1331; VAL-1479; LEU-1592; ARG-1605; GLN-1617; THR-1650; GLU-1801; GLN-1872 AND TRP-1872;

Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy.
Wagnon J.L.; Barker B.S.; Hounshell J.A.; Haaxma C.A.; Shealy A.; Moss T.; Parikh S.; Messer R.D.; Patel M.K.; Meisler M.H.;
Ann. Clin. Transl. Neurol. 3:114-123(2016)
Cited for: VARIANTS DEE13 GLN-1617; GLN-1872; LEU-1872 AND TRP-1872; CHARACTERIZATION OF VARIANTS DEE13 GLN-1617; GLN-1872; LEU-1872 AND TRP-1872; INTERACTION WITH FGF14; GBG3; GBB2 AND SCN1B;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UQD0: Variant p.Arg1872Gln