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NM_001040142.2(SCN2A):c.562C>T (p.Arg188Trp) AND Seizures, benign familial infantile, 3

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 1, 2004
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000013735.27

Allele description [Variation Report for NM_001040142.2(SCN2A):c.562C>T (p.Arg188Trp)]

NM_001040142.2(SCN2A):c.562C>T (p.Arg188Trp)

Gene:
SCN2A:sodium voltage-gated channel alpha subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001040142.2(SCN2A):c.562C>T (p.Arg188Trp)
HGVS:
  • NC_000002.12:g.165308751C>T
  • NG_008143.1:g.74350C>T
  • NM_001040142.2:c.562C>TMANE SELECT
  • NM_001040143.2:c.562C>T
  • NM_001371246.1:c.562C>T
  • NM_001371247.1:c.562C>T
  • NM_021007.3:c.562C>T
  • NP_001035232.1:p.Arg188Trp
  • NP_001035233.1:p.Arg188Trp
  • NP_001358175.1:p.Arg188Trp
  • NP_001358176.1:p.Arg188Trp
  • NP_066287.2:p.Arg188Trp
  • NP_066287.2:p.Arg188Trp
  • NC_000002.11:g.166165261C>T
  • NM_021007.2:c.562C>T
  • Q99250:p.Arg188Trp
Protein change:
R188W; ARG188TRP
Links:
UniProtKB: Q99250#VAR_029733; OMIM: 182390.0001; dbSNP: rs121917748
NCBI 1000 Genomes Browser:
rs121917748
Molecular consequence:
  • NM_001040142.2:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001040143.2:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371246.1:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371247.1:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021007.3:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
  • Decrease in slope of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0072]
  • Moderate hyperpolarizing shift of voltage dependence of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0068]
  • Normal peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0096]
  • Normal rate of recovery from fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0054]
  • Overall gain-of-function [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0137]
  • Slowing of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0048]

Condition(s)

Name:
Seizures, benign familial infantile, 3 (BFIS3)
Synonyms:
CONVULSIONS, BENIGN FAMILIAL INFANTILE, 3; Familial neonatal seizures
Identifiers:
MONDO: MONDO:0011904; MedGen: C1843140; Orphanet: 140927; Orphanet: 306; OMIM: 607745

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000033982OMIM
no assertion criteria provided
Pathogenic
(Apr 1, 2004) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.

Sugawara T, Tsurubuchi Y, Agarwala KL, Ito M, Fukuma G, Mazaki-Miyazaki E, Nagafuji H, Noda M, Imoto K, Wada K, Mitsudome A, Kaneko S, Montal M, Nagata K, Hirose S, Yamakawa K.

Proc Natl Acad Sci U S A. 2001 May 22;98(11):6384-9. Erratum in: Proc Natl Acad Sci U S A 2001 Aug 28;98(18):10515.

PubMed [citation]
PMID:
11371648
PMCID:
PMC33477

Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.

Berkovic SF, Heron SE, Giordano L, Marini C, Guerrini R, Kaplan RE, Gambardella A, Steinlein OK, Grinton BE, Dean JT, Bordo L, Hodgson BL, Yamamoto T, Mulley JC, Zara F, Scheffer IE.

Ann Neurol. 2004 Apr;55(4):550-7.

PubMed [citation]
PMID:
15048894

Details of each submission

From OMIM, SCV000033982.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Sugawara et al. (2001) reported a C-to-T transition in the SCN2A gene, resulting in an arg188-to-trp (R188W) substitution, in a 6-year-old Japanese boy with childhood seizures (BFIS3; 607745) and normal development. He had onset of febrile seizures at age 8 months, and later had 5 episodes of brief afebrile atonic seizures lasting less than 10 seconds since age 4 years. EEG showed single spikes over the right frontal region. Both parents, who were not related, had a history of febrile seizures in childhood. Genetic analysis identified a heterozygous R188W mutation in the boy and the father, but not the mother. In vitro functional expression studies showed that the mutant channel inactivated more slowly than wildtype, whereas channel conductance was not affected. Although Sugawara et al. (2001) suggested a link to GEFS+ (604233), they noted that assignment of the phenotype in this patient was difficult because both parents had febrile seizures, which have a high frequency in the general population. Berkovic et al. (2004) concluded that there is little support for an association between SCN2A and GEFS+, despite the report of Sugawara et al. (2001). Berkovic et al. (2004) also stated that seizures with fever occasionally do occur in BFNIS.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 15, 2024