NM_001165963.4(SCN1A):c.5436G>A (p.Trp1812Ter) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 19, 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:: RCV003588599.2

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5436G>A (p.Trp1812Ter)]

NM_001165963.4(SCN1A):c.5436G>A (p.Trp1812Ter)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.5436G>A (p.Trp1812Ter)

HGVS:

NC_000002.12:g.165991839C>T
NG_011906.1:g.86801G>A
NM_001165963.4:c.5436G>AMANE SELECT
NM_001165964.3:c.5352G>A
NM_001202435.3:c.5436G>A
NM_001353948.2:c.5436G>A
NM_001353949.2:c.5403G>A
NM_001353950.2:c.5403G>A
NM_001353951.2:c.5403G>A
NM_001353952.2:c.5403G>A
NM_001353954.2:c.5400G>A
NM_001353955.2:c.5400G>A
NM_001353957.2:c.5352G>A
NM_001353958.2:c.5352G>A
NM_001353960.2:c.5349G>A
NM_001353961.2:c.2994G>A
NM_006920.6:c.5403G>A
NP_001159435.1:p.Trp1812Ter
NP_001159436.1:p.Trp1784Ter
NP_001189364.1:p.Trp1812Ter
NP_001340877.1:p.Trp1812Ter
NP_001340878.1:p.Trp1801Ter
NP_001340879.1:p.Trp1801Ter
NP_001340880.1:p.Trp1801Ter
NP_001340881.1:p.Trp1801Ter
NP_001340883.1:p.Trp1800Ter
NP_001340884.1:p.Trp1800Ter
NP_001340886.1:p.Trp1784Ter
NP_001340887.1:p.Trp1784Ter
NP_001340889.1:p.Trp1783Ter
NP_001340890.1:p.Trp998Ter
NP_008851.3:p.Trp1801Ter
LRG_8:g.86801G>A
NC_000002.11:g.166848349C>T
NM_001165963.1:c.5436G>A
NR_148667.2:n.5853G>A
AB093548.1:c.5436G>A;p.Trp1812*

Protein change:

W1783*

Links:

dbSNP: rs863225037

NCBI 1000 Genomes Browser:

rs863225037

Molecular consequence:

NR_148667.2:n.5853G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001165963.4:c.5436G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001165964.3:c.5352G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001202435.3:c.5436G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353948.2:c.5436G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353949.2:c.5403G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353950.2:c.5403G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353951.2:c.5403G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353952.2:c.5403G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353954.2:c.5400G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353955.2:c.5400G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353957.2:c.5352G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353958.2:c.5352G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353960.2:c.5349G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353961.2:c.2994G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_006920.6:c.5403G>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

Recent activity

Clear Turn Off Turn On

SRS7649636 (1)
SRA
Pandion haliaetus
Pandion haliaetus
Pandion haliaetus

BioProject
Scyllarides squammosus
Scyllarides squammosus
Scyllarides squammosus RefSeq Genome

BioProject
H.vulgare agpp mRNA for ADP-glucose pyrophosphorylase small subunit
H.vulgare agpp mRNA for ADP-glucose pyrophosphorylase small subunit
gi|18887|emb|X62241.1|

Nucleotide

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
SCV004293419	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 19, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17347258, 28202706, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293419

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 19, 2022)

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

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004293419.1

#	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. ClinVar contains an entry for this variant (Variation ID: 217248). This premature translational stop signal has been observed in individual(s) with SCN1A-related conditions (PMID: 17347258, 28202706). 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.Trp1812*) in the SCN1A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 198 amino acid(s) of the SCN1A protein.

#	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