NM_001165963.4(SCN1A):c.539T>A (p.Leu180Ter) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 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:: RCV001037788.9

Allele description [Variation Report for NM_001165963.4(SCN1A):c.539T>A (p.Leu180Ter)]

NM_001165963.4(SCN1A):c.539T>A (p.Leu180Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.539T>A (p.Leu180Ter)

HGVS:

NC_000002.12:g.166054701A>T
NG_011906.1:g.23939T>A
NM_001165963.4:c.539T>AMANE SELECT
NM_001165963.4:c.539T>A
NM_001165964.3:c.539T>A
NM_001202435.3:c.539T>A
NM_001353948.2:c.539T>A
NM_001353949.2:c.539T>A
NM_001353950.2:c.539T>A
NM_001353951.2:c.539T>A
NM_001353952.2:c.539T>A
NM_001353954.2:c.539T>A
NM_001353955.2:c.539T>A
NM_001353957.2:c.539T>A
NM_001353958.2:c.539T>A
NM_001353960.2:c.539T>A
NM_001353961.2:c.-1887T>A
NM_006920.6:c.539T>A
NP_001159435.1:p.Leu180Ter
NP_001159436.1:p.Leu180Ter
NP_001189364.1:p.Leu180Ter
NP_001340877.1:p.Leu180Ter
NP_001340878.1:p.Leu180Ter
NP_001340879.1:p.Leu180Ter
NP_001340880.1:p.Leu180Ter
NP_001340881.1:p.Leu180Ter
NP_001340883.1:p.Leu180Ter
NP_001340884.1:p.Leu180Ter
NP_001340886.1:p.Leu180Ter
NP_001340887.1:p.Leu180Ter
NP_001340889.1:p.Leu180Ter
NP_008851.3:p.Leu180Ter
LRG_8t1:c.539T>A
LRG_8:g.23939T>A
NC_000002.11:g.166911211A>T
NM_001165963.1:c.539T>A
NM_006920.4:c.539T>A
NR_148667.2:n.925T>A
p.Leu180*

Protein change:

L180*

Links:

dbSNP: rs1574281711

NCBI 1000 Genomes Browser:

rs1574281711

Molecular consequence:

NM_001353961.2:c.-1887T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NR_148667.2:n.925T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001165963.4:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001165964.3:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001202435.3:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353948.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353949.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353950.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353951.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353952.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353954.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353955.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353957.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353958.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353960.2:c.539T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_006920.6:c.539T>A - 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

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Gene ID:125434498

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001201220	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 1, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28202706, 17347258, 18930999, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001201220

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 1, 2020)

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

Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations.

Cetica V, Chiari S, Mei D, Parrini E, Grisotto L, Marini C, Pucatti D, Ferrari A, Sicca F, Specchio N, Trivisano M, Battaglia D, Contaldo I, Zamponi N, Petrelli C, Granata T, Ragona F, Avanzini G, Guerrini R.

Neurology. 2017 Mar 14;88(11):1037-1044. doi: 10.1212/WNL.0000000000003716. Epub 2017 Feb 15.

PubMed [citation]

PMID:: 28202706
PMCID:: PMC5384833

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, SCV001201220.5

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

Description

This nonsense change has been observed in an individual affected with Dravet syndrome (PMID: 28202706). ClinVar contains an entry for this variant (Variation ID: 836613). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu180*) in the SCN1A gene. It is expected to result in an absent or disrupted protein product.

#	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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