NM_001165963.4(SCN1A):c.5870A>G (p.Glu1957Gly) AND Early infantile epileptic encephalopathy with suppression bursts

Clinical significance:Uncertain significance (Last evaluated: Aug 25, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000537890.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5870A>G (p.Glu1957Gly)]

NM_001165963.4(SCN1A):c.5870A>G (p.Glu1957Gly)

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.5870A>G (p.Glu1957Gly)
Other names:
p.E1957G:GAA>GGA
HGVS:
  • NC_000002.12:g.165991405T>C
  • NG_011906.1:g.87235A>G
  • NM_001165963.4:c.5870A>GMANE SELECT
  • NM_001165963.4:c.5870A>G
  • NM_001165964.3:c.5786A>G
  • NM_001202435.3:c.5870A>G
  • NM_001353948.2:c.5870A>G
  • NM_001353949.2:c.5837A>G
  • NM_001353950.2:c.5837A>G
  • NM_001353951.2:c.5837A>G
  • NM_001353952.2:c.5837A>G
  • NM_001353954.2:c.5834A>G
  • NM_001353955.2:c.5834A>G
  • NM_001353957.2:c.5786A>G
  • NM_001353958.2:c.5786A>G
  • NM_001353960.2:c.5783A>G
  • NM_001353961.2:c.3428A>G
  • NM_006920.6:c.5837A>G
  • NP_001159435.1:p.Glu1957Gly
  • NP_001159436.1:p.Glu1929Gly
  • NP_001189364.1:p.Glu1957Gly
  • NP_001340877.1:p.Glu1957Gly
  • NP_001340878.1:p.Glu1946Gly
  • NP_001340879.1:p.Glu1946Gly
  • NP_001340880.1:p.Glu1946Gly
  • NP_001340881.1:p.Glu1946Gly
  • NP_001340883.1:p.Glu1945Gly
  • NP_001340884.1:p.Glu1945Gly
  • NP_001340886.1:p.Glu1929Gly
  • NP_001340887.1:p.Glu1929Gly
  • NP_001340889.1:p.Glu1928Gly
  • NP_001340890.1:p.Glu1143Gly
  • NP_008851.3:p.Glu1946Gly
  • LRG_8t1:c.5837A>G
  • LRG_8:g.87235A>G
  • NC_000002.11:g.166847915T>C
  • NM_001165963.1:c.5870A>G
  • NM_006920.4:c.5837A>G
  • NR_148667.2:n.6287A>G
Protein change:
E1143G
Links:
UniProtKB/Swiss-Prot: VAR_029731; dbSNP: rs121918802
NCBI 1000 Genomes Browser:
rs121918802
Molecular consequence:
  • NM_001165963.4:c.5870A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.5786A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.5870A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.5870A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.5837A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.5837A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.5837A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.5837A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.5834A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.5834A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.5786A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.5786A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.5783A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.3428A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.5837A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.6287A>G - 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
SCV000633877Invitaecriteria provided, single submitter
Uncertain significance
(Aug 25, 2018)
germlineclinical testing

PubMed (4)
[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

UniProt: a hub for protein information.

UniProt Consortium..

Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12. doi: 10.1093/nar/gku989. Epub 2014 Oct 27.

PubMed [citation]
PMID:
25348405
PMCID:
PMC4384041

Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms.

Wallace RH, Hodgson BL, Grinton BE, Gardiner RM, Robinson R, Rodriguez-Casero V, Sadleir L, Morgan J, Harkin LA, Dibbens LM, Yamamoto T, Andermann E, Mulley JC, Berkovic SF, Scheffer IE.

Neurology. 2003 Sep 23;61(6):765-9.

PubMed [citation]
PMID:
14504318
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000633877.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces glutamic acid with glycine at codon 1957 of the SCN1A protein (p.Glu1957Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs121918802, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual with a SCN1A-related disease (PMID: 14504318). ClinVar contains an entry for this variant (Variation ID: 68671). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). This variant identified in the SCN1A gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

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