UniProtKB/SwissProt variant VAR

Variant information

Variant position:

263

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 Alanine (A) to Valine (V) at position 263 (A263V, p.Ala263Val).

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

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

Variant description:

In DEE11 and EA9; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs387906686 [ dbSNP | Ensembl ]

Sequence information

Variant position:

263

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:

QSVKKLSDVMILTVFCLSVF A LIGLQLFMGNLRNKCLQWPP

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                         QSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPP

Mouse                         QSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPP

Rat                           QSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPP

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	251 – 270	Helical; Name=S5 of repeat I
Repeat	111 – 456	I
Helix	251 – 269

Literature citations

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.
Schwarz N.; Hahn A.; Bast T.; Mueller S.; Loeffler H.; Maljevic S.; Gaily E.; Prehl I.; Biskup S.; Joensuu T.; Lehesjoki A.E.; Neubauer B.A.; Lerche H.; Hedrich U.B.;
J. Neurol. 263:334-343(2016)
Cited for: INVOLVEMENT IN EA9; VARIANTS EA9 VAL-263; ALA-1522 AND GLY-1882; CHARACTERIZATION OF VARIANTS EA9 ALA-1522 AND GLY-1882;

SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.
Liao Y.; Anttonen A.K.; Liukkonen E.; Gaily E.; Maljevic S.; Schubert S.; Bellan-Koch A.; Petrou S.; Ahonen V.E.; Lerche H.; Lehesjoki A.E.;
Neurology 75:1454-1458(2010)
Cited for: VARIANT DEE11 VAL-263; CHARACTERIZATION OF VARIANT DEE11 VAL-263;

Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings.
Touma M.; Joshi M.; Connolly M.C.; Grant P.E.; Hansen A.R.; Khwaja O.; Berry G.T.; Kinney H.C.; Poduri A.; Agrawal P.B.;
Epilepsia 54:E81-E85(2013)
Cited for: VARIANT DEE11 VAL-263;

Letter to the editor: confirming neonatal seizure and late onset ataxia in SCN2A Ala263Val.
Johannesen K.M.; Miranda M.J.; Lerche H.; Moeller R.S.;
J. Neurol. 263:1459-1460(2016)
Cited for: VARIANT EA9 VAL-263;

Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes.
Parrini E.; Marini C.; Mei D.; Galuppi A.; Cellini E.; Pucatti D.; Chiti L.; Rutigliano D.; Bianchini C.; Virdo S.; De Vita D.; Bigoni S.; Barba C.; Mari F.; Montomoli M.; Pisano T.; Rosati A.; Guerrini R.;
Hum. Mutat. 38:216-225(2017)
Cited for: VARIANT GLY-191; VARIANTS DEE11 ILE-251; VAL-263; VAL-896; VAL-1316; VAL-1323; TYR-1344; THR-1548 AND GLN-1882;

SCN2A p.Ala263Val Variant a Phenotype of Neonatal Seizures Followed by Paroxysmal Ataxia in Toddlers.
Gorman K.M.; King M.D.;
Pediatr. Neurol. 67:111-112(2017)
Cited for: VARIANT EA9 VAL-263;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99250: Variant p.Ala263Val