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UniProtKB/Swiss-Prot Q99250: Variant p.Leu1330Phe

Sodium channel protein type 2 subunit alpha
Gene: SCN2A
Variant information

Variant position:  1330
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Leucine (L) to Phenylalanine (F) at position 1330 (L1330F, p.Leu1330Phe).
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 medium size and hydrophobic (L) to large size and aromatic (F)
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:  Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant. {ECO:0000269|PubMed:11371648, ECO:0000269|PubMed:12243921, ECO:0000269|PubMed:15048894, ECO:0000269|PubMed:16417554, ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:17386050, ECO:0000269|PubMed:18479388, ECO:0000269|PubMed:20371507, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:23758435, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217}. 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 BFIS3; increased voltage-gated sodium channel activity; decreased overall channel availability during repetitive stimulation; gain of function; no effect on kinetics of activation or inactivation; no effect on voltage dependence of activation.
Any additional useful information about the variant.

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

Sequence information

Variant position:  1330
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2005
The length of the canonical sequence.

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.




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.

Chain 1 – 2005 Sodium channel protein type 2 subunit alpha
Topological domain 1320 – 1336 Cytoplasmic
Repeat 1190 – 1504 III
Helix 1321 – 1330

Literature citations

Sodium-channel defects in benign familial neonatal-infantile seizures.
Heron S.E.; Crossland K.M.; Andermann E.; Phillips H.A.; Hall A.J.; Bleasel A.; Shevell M.; Mercho S.; Seni M.H.; Guiot M.C.; Mulley J.C.; Berkovic S.F.; Scheffer I.E.;
Lancet 360:851-852(2002)
Cited for: VARIANTS BFIS3 PHE-1330 AND VAL-1563;

Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel causing benign familial neonatal-infantile seizures.
Scalmani P.; Rusconi R.; Armatura E.; Zara F.; Avanzini G.; Franceschetti S.; Mantegazza M.;
J. Neurosci. 26:10100-10109(2006)

Impaired NaV1.2 function and reduced cell surface expression in benign familial neonatal-infantile seizures.
Misra S.N.; Kahlig K.M.; George A.L. Jr.;
Epilepsia 49:1535-1545(2008)

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.