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UniProtKB/Swiss-Prot Q9UQD0: Variant p.Val1592Leu

Sodium channel protein type 8 subunit alpha
Gene: SCN8A
Chromosomal location: 12q13.1
Variant information

Variant position:  1592
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 Valine (V) to Leucine (L) at position 1592 (V1592L, p.Val1592Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

Involvement in disease:  Epileptic encephalopathy, early infantile, 13 (EIEE13) [MIM:614558]: A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. EIEE13 is a severe form consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy. {ECO:0000269|PubMed:22365152, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:24352161, ECO:0000269|PubMed:24874546, ECO:0000269|PubMed:24888894, ECO:0000269|PubMed:25239001, ECO:0000269|PubMed:25568300, ECO:0000269|PubMed:25725044, ECO:0000269|PubMed:25785782, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26900580, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27210545, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28923014}. 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 EIEE13; unknown pathological significance.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  1592
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:   KMFALRHYYFTIGWNIFDFV  V VILSIVGMFLADIIEKYFVS
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                         KMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVS

Mouse                         KMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVS

Rat                           KMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVS

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.

TypePositionsDescription
Chain 1 – 1980 Sodium channel protein type 8 subunit alpha
Transmembrane 1584 – 1601 Helical; Name=S3 of repeat IV
Repeat 1504 – 1801 IV
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 EIEE13 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;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.