NM_001165963.4(SCN1A):c.257del (p.Asn86fs) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 9, 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:: RCV003754783.2

Allele description [Variation Report for NM_001165963.4(SCN1A):c.257del (p.Asn86fs)]

NM_001165963.4(SCN1A):c.257del (p.Asn86fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.257del (p.Asn86fs)

HGVS:

NC_000002.12:g.166073366del
NG_011906.1:g.5275del
NM_001165963.4:c.257delMANE SELECT
NM_001165964.3:c.257del
NM_001202435.3:c.257del
NM_001353948.2:c.257del
NM_001353949.2:c.257del
NM_001353950.2:c.257del
NM_001353951.2:c.257del
NM_001353952.2:c.257del
NM_001353954.2:c.257del
NM_001353955.2:c.257del
NM_001353957.2:c.257del
NM_001353958.2:c.257del
NM_001353960.2:c.257del
NM_001353961.2:c.-2169del
NM_006920.6:c.257del
NP_001159435.1:p.Asn86fs
NP_001159436.1:p.Asn86fs
NP_001189364.1:p.Asn86fs
NP_001340877.1:p.Asn86fs
NP_001340878.1:p.Asn86fs
NP_001340879.1:p.Asn86fs
NP_001340880.1:p.Asn86fs
NP_001340881.1:p.Asn86fs
NP_001340883.1:p.Asn86fs
NP_001340884.1:p.Asn86fs
NP_001340886.1:p.Asn86fs
NP_001340887.1:p.Asn86fs
NP_001340889.1:p.Asn86fs
NP_008851.3:p.Asn86Ilefs
NP_008851.3:p.Asn86fs
LRG_8t1:c.256del
LRG_8:g.5275del
LRG_8p1:p.Asn86Ilefs
NC_000002.11:g.166929875del
NC_000002.11:g.166929876del
NM_006920.4:c.256delA
NR_148667.2:n.643del

Protein change:

N86fs

Molecular consequence:

NM_001353961.2:c.-2169del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001165964.3:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001202435.3:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353948.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353949.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353950.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353951.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353952.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353954.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353955.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353957.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353958.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353960.2:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006920.6:c.257del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_148667.2:n.643del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

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AAB25189 (0)
OMIM
Loligo forbesii voucher haplotype 22 cytochrome c oxidase subunit I (COX1) gene,...
Loligo forbesii voucher haplotype 22 cytochrome c oxidase subunit I (COX1) gene, partial cds; mitochondrial
gi|2095208868|gb|OK135765.1|

Nucleotide
PsbA, partial (chloroplast) [Salix hookeriana]
PsbA, partial (chloroplast) [Salix hookeriana]
gi|667488355|gb|AIG58477.1|

Protein
ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, partial (chloropl...
ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, partial (chloroplast) [Salix hookeriana]
gi|1024263241|gb|ANB49818.1|

Protein
Cerambycidae 18S ribosomal RNA gene, partial sequence.
Cerambycidae 18S ribosomal RNA gene, partial sequence.
PopSet: 1383781417

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004457099	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 9, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17347258, 18930999, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004457099

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 9, 2023)

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

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

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004457099.1

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

Description

For these reasons, this variant has been classified as Pathogenic. 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 sequence change creates a premature translational stop signal (p.Asn86Ilefs*6) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. 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: Sep 29, 2024

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