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NM_001165963.4(SCN1A):c.4284+1G>T AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 27, 2023
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:
RCV000636436.8

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4284+1G>T]

NM_001165963.4(SCN1A):c.4284+1G>T

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.4284+1G>T
HGVS:
  • NC_000002.12:g.166002471C>A
  • NG_011906.1:g.76169G>T
  • NM_001165963.4:c.4284+1G>TMANE SELECT
  • NM_001165964.3:c.4200+1G>T
  • NM_001202435.3:c.4284+1G>T
  • NM_001353948.2:c.4284+1G>T
  • NM_001353949.2:c.4251+1G>T
  • NM_001353950.2:c.4251+1G>T
  • NM_001353951.2:c.4251+1G>T
  • NM_001353952.2:c.4251+1G>T
  • NM_001353954.2:c.4248+1G>T
  • NM_001353955.2:c.4248+1G>T
  • NM_001353957.2:c.4200+1G>T
  • NM_001353958.2:c.4200+1G>T
  • NM_001353960.2:c.4197+1G>T
  • NM_001353961.2:c.1842+1G>T
  • NM_006920.6:c.4251+1G>T
  • LRG_8:g.76169G>T
  • NC_000002.11:g.166858981C>A
  • NM_001165963.1:c.4284+1G>T
Links:
dbSNP: rs1553524865
NCBI 1000 Genomes Browser:
rs1553524865
Molecular consequence:
  • NM_001165963.4:c.4284+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001165964.3:c.4200+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001202435.3:c.4284+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353948.2:c.4284+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353949.2:c.4251+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353950.2:c.4251+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353951.2:c.4251+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353952.2:c.4251+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353954.2:c.4248+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353955.2:c.4248+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353957.2:c.4200+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353958.2:c.4200+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353960.2:c.4197+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001353961.2:c.1842+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_006920.6:c.4251+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
SCV000757875Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 27, 2023) 		germlineclinical testing

PubMed (5)
[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

Genotype-phenotype associations in SCN1A-related epilepsies.

Zuberi SM, Brunklaus A, Birch R, Reavey E, Duncan J, Forbes GH.

Neurology. 2011 Feb 15;76(7):594-600. doi: 10.1212/WNL.0b013e31820c309b. Epub 2011 Jan 19.

PubMed [citation]
PMID:
21248271

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000757875.4

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 530534). Disruption of this splice site has been observed in individual(s) with classic Dravet syndrome (PMID: 21248271). 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 21 of the SCN1A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999).

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

Last Updated: Sep 29, 2024