UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1522

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

Type of variant:

Unclassified

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 Alanine (A) at position 1522 (G1522A, p.Gly1522Ala).

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 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, 11 (EIEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25459969, ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29625812, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217, ECO:0000269|PubMed:30415926}. 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 found in a patient with neonatal epilepsy with late-onset episodic ataxia and EIEE11; unknown pathological significance; no effect voltage-gated sodium channel activity; higher current density when associated with G-1882; unknown pathological significance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs147522594 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1522

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:

KKLGSKKPQKPIPRPANKFQ G MVFDFVTKQVFDISIMILIC

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                         KKLGSKKPQKPIPRPANKFQGMVFDFVTKQVFDISIMILIC

Mouse                         KKLGSKKPQKPIPRPANKFQGMVFDFVTKQVFDISIMILIC

Rat                           KKLGSKKPQKPIPRPANKFQGMVFDFVTKQVFDISIMILIC

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
Topological domain	1470 – 1532	Cytoplasmic
Repeat	1513 – 1811	IV
Modified residue	1506 – 1506	Phosphoserine; by PKC
Helix	1520 – 1528

Literature citations

Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.
Mercimek-Mahmutoglu S.; Patel J.; Cordeiro D.; Hewson S.; Callen D.; Donner E.J.; Hahn C.D.; Kannu P.; Kobayashi J.; Minassian B.A.; Moharir M.; Siriwardena K.; Weiss S.K.; Weksberg R.; Snead O.C. III;
Epilepsia 56:707-716(2015)
Cited for: VARIANTS EIEE11 GLY-220 AND ALA-1522;

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: VARIANTS VAL-263; ALA-1522 AND GLY-1882; CHARACTERIZATION OF VARIANTS ALA-1522 AND GLY-1882;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99250: Variant p.Gly1522Ala