NM_001165963.4(SCN1A):c.4298G>A (p.Gly1433Glu) AND Early infantile epileptic encephalopathy with suppression bursts

Clinical significance:Pathogenic (Last evaluated: Jul 30, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001067468.2

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4298G>A (p.Gly1433Glu)]

NM_001165963.4(SCN1A):c.4298G>A (p.Gly1433Glu)

Genes:
SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001165963.4(SCN1A):c.4298G>A (p.Gly1433Glu)
HGVS:
  • NC_000002.12:g.165999763C>T
  • NG_011906.1:g.78877G>A
  • NM_001165963.4:c.4298G>AMANE SELECT
  • NM_001165963.4:c.4298G>A
  • NM_001165964.3:c.4214G>A
  • NM_001202435.3:c.4298G>A
  • NM_001353948.2:c.4298G>A
  • NM_001353949.2:c.4265G>A
  • NM_001353950.2:c.4265G>A
  • NM_001353951.2:c.4265G>A
  • NM_001353952.2:c.4265G>A
  • NM_001353954.2:c.4262G>A
  • NM_001353955.2:c.4262G>A
  • NM_001353957.2:c.4214G>A
  • NM_001353958.2:c.4214G>A
  • NM_001353960.2:c.4211G>A
  • NM_001353961.2:c.1856G>A
  • NM_006920.6:c.4265G>A
  • NP_001159435.1:p.Gly1433Glu
  • NP_001159436.1:p.Gly1405Glu
  • NP_001189364.1:p.Gly1433Glu
  • NP_001340877.1:p.Gly1433Glu
  • NP_001340878.1:p.Gly1422Glu
  • NP_001340879.1:p.Gly1422Glu
  • NP_001340880.1:p.Gly1422Glu
  • NP_001340881.1:p.Gly1422Glu
  • NP_001340883.1:p.Gly1421Glu
  • NP_001340884.1:p.Gly1421Glu
  • NP_001340886.1:p.Gly1405Glu
  • NP_001340887.1:p.Gly1405Glu
  • NP_001340889.1:p.Gly1404Glu
  • NP_001340890.1:p.Gly619Glu
  • NP_008851.3:p.Gly1422Glu
  • LRG_8t1:c.4265G>A
  • LRG_8:g.78877G>A
  • NC_000002.11:g.166856273C>T
  • NM_001165963.1:c.4298G>A
  • NM_006920.4:c.4265G>A
  • NR_148667.2:n.4715G>A
Protein change:
G1404E
Links:
UniProtKB/Swiss-Prot: VAR_064261; dbSNP: rs121918741
NCBI 1000 Genomes Browser:
rs121918741
Molecular consequence:
  • NM_001165963.4:c.4298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.4214G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.4298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.4298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.4265G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.4265G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.4265G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.4265G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.4262G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.4262G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.4214G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.4214G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.4211G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.1856G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.4265G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.4715G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:
Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:
MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001232534Invitaecriteria provided, single submitter
Pathogenic
(Jul 30, 2019)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Prevalence of SCN1A-related dravet syndrome among children reported with seizures following vaccination: a population-based ten-year cohort study.

Verbeek NE, van der Maas NA, Jansen FE, van Kempen MJ, Lindhout D, Brilstra EH.

PLoS One. 2013 Jun 6;8(6):e65758. doi: 10.1371/journal.pone.0065758. Print 2013.

PubMed [citation]
PMID:
23762420
PMCID:
PMC3675088

Seven novel SCN1A mutations in Chinese patients with severe myoclonic epilepsy of infancy.

Sun H, Zhang Y, Liang J, Liu X, Ma X, Qin J, Qi Y, Wu X.

Epilepsia. 2008 Jun;49(6):1104-7. doi: 10.1111/j.1528-1167.2008.01549_2.x. No abstract available.

PubMed [citation]
PMID:
18554359
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001232534.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces glycine with glutamic acid at codon 1433 of the SCN1A protein (p.Gly1433Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with Dravet syndrome (PMID: 23762420, 18554359). ClinVar contains an entry for this variant (Variation ID: 68630). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Gly1433 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID:21248271, 20729507), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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