NM_001165963.4(SCN1A):c.3879+5G>T AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 18, 2022
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:: RCV001216784.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.3879+5G>T]

NM_001165963.4(SCN1A):c.3879+5G>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.3879+5G>T

HGVS:

NC_000002.12:g.166012104C>A
NG_011906.1:g.66536G>T
NM_001165963.3:c.3879+5G>T
NM_001165963.4:c.3879+5G>TMANE SELECT
NM_001165964.3:c.3795+5G>T
NM_001202435.3:c.3879+5G>T
NM_001353948.2:c.3879+5G>T
NM_001353949.2:c.3846+5G>T
NM_001353950.2:c.3846+5G>T
NM_001353951.2:c.3846+5G>T
NM_001353952.2:c.3846+5G>T
NM_001353954.2:c.3843+5G>T
NM_001353955.2:c.3843+5G>T
NM_001353957.2:c.3795+5G>T
NM_001353958.2:c.3795+5G>T
NM_001353960.2:c.3792+5G>T
NM_001353961.2:c.1437+5G>T
NM_006920.6:c.3846+5G>T
LRG_8:g.66536G>T
NC_000002.11:g.166868614C>A
NM_001165963.1:c.3879+5G>T
NM_001165963.4:c.3879+5G>T

Links:

dbSNP: rs796052999

NCBI 1000 Genomes Browser:

rs796052999

Molecular consequence:

NM_001165963.4:c.3879+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001165964.3:c.3795+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001202435.3:c.3879+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353948.2:c.3879+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353949.2:c.3846+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353950.2:c.3846+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353951.2:c.3846+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353952.2:c.3846+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353954.2:c.3843+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353955.2:c.3843+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353957.2:c.3795+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353958.2:c.3795+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353960.2:c.3792+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001353961.2:c.1437+5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_006920.6:c.3846+5G>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001388596	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 18, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34338318, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001388596

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 18, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Defining Dravet syndrome: An essential pre-requisite for precision medicine trials.

Li W, Schneider AL, Scheffer IE.

Epilepsia. 2021 Sep;62(9):2205-2217. doi: 10.1111/epi.17015. Epub 2021 Aug 2.

PubMed [citation]

PMID:: 34338318
PMCID:: PMC9291974

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001388596.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change falls in intron 19 of the SCN1A gene. It does not directly change the encoded amino acid sequence of the SCN1A protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Dravet syndrome (PMID: 34338318). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 946012). Variants that disrupt 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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Relating variation to medicine