NM_001165963.4(SCN1A):c.4563_4581+39del AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 4, 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:: RCV000699910.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4563_4581+39del]

NM_001165963.4(SCN1A):c.4563_4581+39del

Genes:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]

Variant type:

Deletion

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.4563_4581+39del

HGVS:

NC_000002.12:g.165995978_165996035del
NG_011906.1:g.82609_82666del
NM_001165963.4:c.4563_4581+39delMANE SELECT
NM_001165964.3:c.4479_4497+39del
NM_001202435.3:c.4563_4581+39del
NM_001353948.2:c.4563_4581+39del
NM_001353949.2:c.4530_4548+39del
NM_001353950.2:c.4530_4548+39del
NM_001353951.2:c.4530_4548+39del
NM_001353952.2:c.4530_4548+39del
NM_001353954.2:c.4527_4545+39del
NM_001353955.2:c.4527_4545+39del
NM_001353957.2:c.4479_4497+39del
NM_001353958.2:c.4479_4497+39del
NM_001353960.2:c.4476_4494+39del
NM_001353961.2:c.2121_2139+39del
NM_006920.6:c.4530_4548+39del
LRG_8:g.82609_82666del
NC_000002.11:g.166852484_166852541del
NC_000002.11:g.166852488_166852545del
NM_001165963.1:c.4563_4581+39delGCCTATACCTCGACCAGGAGTAAGAAGTATCAAATGATATGGGGGAAAAATACAAAAA

Links:

dbSNP: rs1559114202

NCBI 1000 Genomes Browser:

rs1559114202

Molecular consequence:

NM_001165963.4:c.4563_4581+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001165964.3:c.4479_4497+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001202435.3:c.4563_4581+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353948.2:c.4563_4581+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353949.2:c.4530_4548+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353950.2:c.4530_4548+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353951.2:c.4530_4548+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353952.2:c.4530_4548+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353954.2:c.4527_4545+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353955.2:c.4527_4545+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353957.2:c.4479_4497+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353958.2:c.4479_4497+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353960.2:c.4476_4494+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353961.2:c.2121_2139+39del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_006920.6:c.4530_4548+39del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000828641	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 4, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 17347258, 18930999, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000828641

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 4, 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

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

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 (4)

Details of each submission

From Invitae, SCV000828641.4

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

Description

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. ClinVar contains an entry for this variant (Variation ID: 577218). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant results in the deletion of part of exon 24 (c.4563_4581+39del) 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).

#	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: Feb 14, 2024

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