UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1319

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 Arginine (R) to Glutamine (Q) at position 1319 (R1319Q, p.Arg1319Gln).

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

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}. 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; modified voltage-gated sodium channel activity; modified voltage dependence of activation and inactivation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121917753 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1319

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:

LGAIKSLRTLRALRPLRALS R FEGMRVVVNALLGAIPSIMN

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                         LGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMN

Rat                           LGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMN

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	1301 – 1319	Helical; Name=S4 of repeat III
Repeat	1190 – 1504	III

Literature citations

Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.
Berkovic S.F.; Heron S.E.; Giordano L.; Marini C.; Guerrini R.; Kaplan R.E.; Gambardella A.; Steinlein O.K.; Grinton B.E.; Dean J.T.; Bordo L.; Hodgson B.L.; Yamamoto T.; Mulley J.C.; Zara F.; Scheffer I.E.;
Ann. Neurol. 55:550-557(2004)
Cited for: VARIANTS BFIS3 GLN-223; ILE-892; ILE-1003 AND GLN-1319;

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)
Cited for: CHARACTERIZATION OF VARIANTS BFIS3 GLN-223; GLN-1319; PHE-1330 AND VAL-1563; FUNCTION;

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)
Cited for: CHARACTERIZATION OF VARIANTS BFIS3 GLN-1319; PHE-1330 AND VAL-1563;

Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance.
Zara F.; Specchio N.; Striano P.; Robbiano A.; Gennaro E.; Paravidino R.; Vanni N.; Beccaria F.; Capovilla G.; Bianchi A.; Caffi L.; Cardilli V.; Darra F.; Bernardina B.D.; Fusco L.; Gaggero R.; Giordano L.; Guerrini R.; Incorpora G.; Mastrangelo M.; Spaccini L.; Laverda A.M.; Vecchi M.; Vanadia F.; Veggiotti P.; Viri M.; Occhi G.; Budetta M.; Taglialatela M.; Coviello D.A.; Vigevano F.; Minetti C.;
Epilepsia 54:425-436(2013)
Cited for: VARIANTS BFIS3 GLN-223; LYS-1001; GLN-1319 AND ASN-1641;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99250: Variant p.Arg1319Gln