NM_001165963.4(SCN1A):c.4244_4245del (p.Asn1414_Phe1415insTer) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 23, 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:: RCV002517631.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4244_4245del (p.Asn1414_Phe1415insTer)]

NM_001165963.4(SCN1A):c.4244_4245del (p.Asn1414_Phe1415insTer)

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.4244_4245del (p.Asn1414_Phe1415insTer)

HGVS:

NC_000002.12:g.166002512_166002513del
NG_011906.1:g.76128_76129del
NM_001165963.4:c.4244_4245delMANE SELECT
NM_001165964.3:c.4160_4161del
NM_001202435.3:c.4244_4245del
NM_001353948.2:c.4244_4245del
NM_001353949.2:c.4211_4212del
NM_001353950.2:c.4211_4212del
NM_001353951.2:c.4211_4212del
NM_001353952.2:c.4211_4212del
NM_001353954.2:c.4208_4209del
NM_001353955.2:c.4208_4209del
NM_001353957.2:c.4160_4161del
NM_001353958.2:c.4160_4161del
NM_001353960.2:c.4157_4158del
NM_001353961.2:c.1802_1803del
NM_006920.6:c.4211_4212del
NP_001159435.1:p.Asn1414_Phe1415insTer
NP_001159436.1:p.Asn1386_Phe1387insTer
NP_001189364.1:p.Asn1414_Phe1415insTer
NP_001340877.1:p.Asn1414_Phe1415insTer
NP_001340878.1:p.Asn1403_Phe1404insTer
NP_001340879.1:p.Asn1403_Phe1404insTer
NP_001340880.1:p.Asn1403_Phe1404insTer
NP_001340881.1:p.Asn1403_Phe1404insTer
NP_001340883.1:p.Asn1402_Phe1403insTer
NP_001340884.1:p.Asn1402_Phe1403insTer
NP_001340886.1:p.Asn1386_Phe1387insTer
NP_001340887.1:p.Asn1386_Phe1387insTer
NP_001340889.1:p.Asn1385_Phe1386insTer
NP_001340890.1:p.Asn600_Phe601insTer
NP_008851.3:p.Asn1403_Phe1404insTer
LRG_8:g.76128_76129del
NC_000002.11:g.166859021_166859022del
NC_000002.11:g.166859022_166859023del
NM_001165963.1:c.4244_4245delTT
NR_148667.2:n.4661_4662del

Links:

dbSNP: rs794726705

NCBI 1000 Genomes Browser:

rs794726705

Molecular consequence:

NR_148667.2:n.4661_4662del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001165963.4:c.4244_4245del - nonsense - [Sequence Ontology: SO:0001587]
NM_001165964.3:c.4160_4161del - nonsense - [Sequence Ontology: SO:0001587]
NM_001202435.3:c.4244_4245del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353948.2:c.4244_4245del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353949.2:c.4211_4212del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353950.2:c.4211_4212del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353951.2:c.4211_4212del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353952.2:c.4211_4212del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353954.2:c.4208_4209del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353955.2:c.4208_4209del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353957.2:c.4160_4161del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353958.2:c.4160_4161del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353960.2:c.4157_4158del - nonsense - [Sequence Ontology: SO:0001587]
NM_001353961.2:c.1802_1803del - nonsense - [Sequence Ontology: SO:0001587]
NM_006920.6:c.4211_4212del - nonsense - [Sequence Ontology: SO:0001587]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003525064	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 23, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20431604, 17347258, 18930999, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525064

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 23, 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

Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome.

Sun H, Zhang Y, Liu X, Ma X, Yang Z, Qin J, Jiang Y, Qi Y, Wu X.

J Hum Genet. 2010 Jul;55(7):421-7. doi: 10.1038/jhg.2010.39. Epub 2010 Apr 30.

PubMed [citation]

PMID:: 20431604

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003525064.2

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189854). This premature translational stop signal has been observed in individual(s) with Dravet syndrome (PMID: 20431604). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe1415*) 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

ClinVar

Relating variation to medicine