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NM_001165963.4(SCN1A):c.2946+1G>T AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 27, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001850419.4

Allele description [Variation Report for NM_001165963.4(SCN1A):c.2946+1G>T]

NM_001165963.4(SCN1A):c.2946+1G>T

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_001165963.4(SCN1A):c.2946+1G>T
HGVS:
  • NC_000002.12:g.166037775C>A
  • NG_011906.1:g.40865G>T
  • NM_001165963.4:c.2946+1G>TMANE SELECT
  • NM_001165964.3:c.2862+1G>T
  • NM_001202435.3:c.2946+1G>T
  • NM_001353948.2:c.2946+1G>T
  • NM_001353949.2:c.2913+1G>T
  • NM_001353950.2:c.2913+1G>T
  • NM_001353951.2:c.2913+1G>T
  • NM_001353952.2:c.2913+1G>T
  • NM_001353954.2:c.2910+1G>T
  • NM_001353955.2:c.2910+1G>T
  • NM_001353957.2:c.2862+1G>T
  • NM_001353958.2:c.2862+1G>T
  • NM_001353960.2:c.2859+1G>T
  • NM_001353961.2:c.504+1G>T
  • NM_006920.6:c.2913+1G>T
  • LRG_8:g.40865G>T
  • NC_000002.11:g.166894285C>A
  • NM_001165963.1:c.2946+1G>T
Links:
dbSNP: rs794726772
NCBI 1000 Genomes Browser:
rs794726772
Molecular consequence:
  • NM_001165963.4:c.2946+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001165964.3:c.2862+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001202435.3:c.2946+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353948.2:c.2946+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353949.2:c.2913+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353950.2:c.2913+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353951.2:c.2913+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353952.2:c.2913+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353954.2:c.2910+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353955.2:c.2910+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353957.2:c.2862+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353958.2:c.2862+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353960.2:c.2859+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353961.2:c.504+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_006920.6:c.2913+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002151685Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 27, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Evaluation of the effect of c.2946+1G>T mutation on splicing in the SCN1A gene.

Ben Mahmoud A, Ben Mansour R, Driss F, Baklouti-Gargouri S, Siala O, Mkaouar-Rebai E, Fakhfakh F.

Comput Biol Chem. 2015 Feb;54:44-8. doi: 10.1016/j.compbiolchem.2015.01.003. Epub 2015 Jan 5.

PubMed [citation]
PMID:
25590135

The spectrum of SCN1A-related infantile epileptic encephalopathies.

Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, Sadleir LG, Andermann E, Gill D, Farrell K, Connolly M, Stanley T, Harbord M, Andermann F, Wang J, Batish SD, Jones JG, Seltzer WK, Gardner A; Infantile Epileptic Encephalopathy Referral Consortium., Sutherland G, Berkovic SF, et al.

Brain. 2007 Mar;130(Pt 3):843-52.

PubMed [citation]
PMID:
17347258
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002151685.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 15, but is expected to preserve the integrity of the reading-frame (PMID: 25590135). ClinVar contains an entry for this variant (Variation ID: 189935). Disruption of this splice site has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 17347258). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 15 of the SCN1A gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product.

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

Last Updated: Feb 14, 2024