NM_001165963.4(SCN1A):c.1659_1660insT (p.Gln554fs) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 2, 2020
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:: RCV001381107.4

Allele description [Variation Report for NM_001165963.4(SCN1A):c.1659_1660insT (p.Gln554fs)]

NM_001165963.4(SCN1A):c.1659_1660insT (p.Gln554fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.1659_1660insT (p.Gln554fs)

HGVS:

NC_000002.12:g.166045045_166045046insA
NG_011906.1:g.33594_33595insT
NM_001165963.4:c.1659_1660insTMANE SELECT
NM_001165964.3:c.1659_1660insT
NM_001202435.3:c.1659_1660insT
NM_001353948.2:c.1659_1660insT
NM_001353949.2:c.1659_1660insT
NM_001353950.2:c.1659_1660insT
NM_001353951.2:c.1659_1660insT
NM_001353952.2:c.1659_1660insT
NM_001353954.2:c.1656_1657insT
NM_001353955.2:c.1656_1657insT
NM_001353957.2:c.1659_1660insT
NM_001353958.2:c.1659_1660insT
NM_001353960.2:c.1656_1657insT
NM_001353961.2:c.-767_-766insT
NM_006920.6:c.1659_1660insT
NP_001159435.1:p.Gln554fs
NP_001159436.1:p.Gln554fs
NP_001189364.1:p.Gln554fs
NP_001340877.1:p.Gln554fs
NP_001340878.1:p.Gln554fs
NP_001340879.1:p.Gln554fs
NP_001340880.1:p.Gln554fs
NP_001340881.1:p.Gln554fs
NP_001340883.1:p.Gln553fs
NP_001340884.1:p.Gln553fs
NP_001340886.1:p.Gln554fs
NP_001340887.1:p.Gln554fs
NP_001340889.1:p.Gln553fs
NP_008851.3:p.Gln554fs
LRG_8:g.33594_33595insT
NC_000002.11:g.166901555_166901556insA
NR_148667.2:n.2045_2046insT

Protein change:

Q553fs

Links:

dbSNP: rs2105849998

NCBI 1000 Genomes Browser:

rs2105849998

Molecular consequence:

NM_001353961.2:c.-767_-766insT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001165964.3:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001202435.3:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353948.2:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353949.2:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353950.2:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353951.2:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353952.2:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353954.2:c.1656_1657insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353955.2:c.1656_1657insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353957.2:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353958.2:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353960.2:c.1656_1657insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006920.6:c.1659_1660insT - frameshift variant - [Sequence Ontology: SO:0001589]
NR_148667.2:n.2045_2046insT - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001579359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 2, 2020)	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

SCV001579359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 2, 2020)

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, SCV001579359.2

#	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 creates a premature translational stop signal (p.Gln554Serfs*17) in the SCN1A gene. It is expected to result 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 conditions. 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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