NM_006920.6(SCN1A):c.264+5G>C AND Early infantile epileptic encephalopathy with suppression bursts

Clinical significance:Pathogenic (Last evaluated: May 15, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001212061.2

Allele description [Variation Report for NM_006920.6(SCN1A):c.264+5G>C]

NM_006920.6(SCN1A):c.264+5G>C

Gene:
SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_006920.6(SCN1A):c.264+5G>C
HGVS:
  • NC_000002.12:g.166073353C>G
  • NG_011906.1:g.5287G>C
  • NM_001165963.3:c.264+5G>C
  • NM_001165964.3:c.264+5G>C
  • NM_001202435.3:c.264+5G>C
  • NM_001353948.2:c.264+5G>C
  • NM_001353949.2:c.264+5G>C
  • NM_001353950.2:c.264+5G>C
  • NM_001353951.2:c.264+5G>C
  • NM_001353952.2:c.264+5G>C
  • NM_001353954.2:c.264+5G>C
  • NM_001353955.2:c.264+5G>C
  • NM_001353957.2:c.264+5G>C
  • NM_001353958.2:c.264+5G>C
  • NM_001353960.2:c.264+5G>C
  • NM_001353961.2:c.-2162+5G>C
  • NM_006920.6:c.264+5G>C
  • LRG_8:g.5287G>C
  • NC_000002.11:g.166929863C>G
  • NM_001165963.1:c.264+5G>C
Links:
dbSNP: rs794726762
NCBI 1000 Genomes Browser:
rs794726762
Molecular consequence:
  • NM_001165963.3:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001165964.3:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001202435.3:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353948.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353949.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353950.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353951.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353952.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353954.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353955.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353957.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353958.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353960.2:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353961.2:c.-2162+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_006920.6:c.264+5G>C - intron variant - [Sequence Ontology: SO:0001627]

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001383634Invitaecriteria provided, single submitter
Pathogenic
(May 15, 2019)
germlineclinical testing

PubMed (6)
[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

Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "de novo" SCN1A Mutations in Children with Dravet Syndrome.

Xu X, Yang X, Wu Q, Liu A, Yang X, Ye AY, Huang AY, Li J, Wang M, Yu Z, Wang S, Zhang Z, Wu X, Wei L, Zhang Y.

Hum Mutat. 2015 Sep;36(9):861-72. doi: 10.1002/humu.22819. Epub 2015 Jul 24.

PubMed [citation]
PMID:
26096185
PMCID:
PMC5034833

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001383634.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change falls in intron 1 of the SCN1A gene. It does not directly change the encoded amino acid sequence of the SCN1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Dravet syndrome (PMID: 26096185). ClinVar contains an entry for this variant (Variation ID: 189925). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the c.264+2G nucleotide in the SCN1A gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 25669891,17054684). This suggests that this nucleotide is clinically-significant, and that variants that disrupt this position are likely to be disease-causing. 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: Oct 8, 2021

Support Center