NM_001165963.4(SCN1A):c.3880-2A>G AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 8, 2018
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:: RCV000707470.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.3880-2A>G]

NM_001165963.4(SCN1A):c.3880-2A>G

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.3880-2A>G

HGVS:

NC_000002.12:g.166009843T>C
NG_011906.1:g.68797A>G
NM_001165963.4:c.3880-2A>GMANE SELECT
NM_001165964.3:c.3796-2A>G
NM_001202435.3:c.3880-2A>G
NM_001353948.2:c.3880-2A>G
NM_001353949.2:c.3847-2A>G
NM_001353950.2:c.3847-2A>G
NM_001353951.2:c.3847-2A>G
NM_001353952.2:c.3847-2A>G
NM_001353954.2:c.3844-2A>G
NM_001353955.2:c.3844-2A>G
NM_001353957.2:c.3796-2A>G
NM_001353958.2:c.3796-2A>G
NM_001353960.2:c.3793-2A>G
NM_001353961.2:c.1438-2A>G
NM_006920.6:c.3847-2A>G
LRG_8:g.68797A>G
NC_000002.11:g.166866353T>C
NM_001165963.1:c.3880-2A>G

Links:

dbSNP: rs794726816

NCBI 1000 Genomes Browser:

rs794726816

Molecular consequence:

NM_001165963.4:c.3880-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001165964.3:c.3796-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001202435.3:c.3880-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353948.2:c.3880-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353949.2:c.3847-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353950.2:c.3847-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353951.2:c.3847-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353952.2:c.3847-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353954.2:c.3844-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353955.2:c.3844-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353957.2:c.3796-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353958.2:c.3796-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353960.2:c.3793-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353961.2:c.1438-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_006920.6:c.3847-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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TSA: Hypotaenidia okinawae RNA, GAOK12710, transcribed RNA sequence
TSA: Hypotaenidia okinawae RNA, GAOK12710, transcribed RNA sequence
gi|1820480599|dbj|ICPP01012697.1||g A:ICPP01|GAOK12710

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000836569	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18930999, 17347258, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000836569

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2018)

germline

clinical testing

PubMed (3)
[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

Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients.

Depienne C, Trouillard O, Saint-Martin C, Gourfinkel-An I, Bouteiller D, Carpentier W, Keren B, Abert B, Gautier A, Baulac S, Arzimanoglou A, Cazeneuve C, Nabbout R, LeGuern E.

J Med Genet. 2009 Mar;46(3):183-91. doi: 10.1136/jmg.2008.062323. Epub 2008 Oct 17.

PubMed [citation]

PMID:: 18930999

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000836569.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change affects an acceptor splice site in intron 19 of the SCN1A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN1A-related disease. However, family studies have indicated that this variant was not present in the parents of an individual with clinical features consistent with a SCN1A-related disease, which suggests that it was de novo in that affected individual (Invitae). ClinVar contains an entry for this variant (Variation ID: 189985). 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. Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as 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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