NM_001165963.4(SCN1A):c.1150T>A (p.Trp384Arg) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 22, 2017
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:: RCV000636430.8

Allele description [Variation Report for NM_001165963.4(SCN1A):c.1150T>A (p.Trp384Arg)]

NM_001165963.4(SCN1A):c.1150T>A (p.Trp384Arg)

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.1150T>A (p.Trp384Arg)

HGVS:

NC_000002.12:g.166047647A>T
NG_011906.1:g.30993T>A
NM_001165963.4:c.1150T>AMANE SELECT
NM_001165964.3:c.1150T>A
NM_001202435.3:c.1150T>A
NM_001353948.2:c.1150T>A
NM_001353949.2:c.1150T>A
NM_001353950.2:c.1150T>A
NM_001353951.2:c.1150T>A
NM_001353952.2:c.1150T>A
NM_001353954.2:c.1150T>A
NM_001353955.2:c.1150T>A
NM_001353957.2:c.1150T>A
NM_001353958.2:c.1150T>A
NM_001353960.2:c.1150T>A
NM_001353961.2:c.-1276T>A
NM_006920.6:c.1150T>A
NP_001159435.1:p.Trp384Arg
NP_001159436.1:p.Trp384Arg
NP_001189364.1:p.Trp384Arg
NP_001340877.1:p.Trp384Arg
NP_001340878.1:p.Trp384Arg
NP_001340879.1:p.Trp384Arg
NP_001340880.1:p.Trp384Arg
NP_001340881.1:p.Trp384Arg
NP_001340883.1:p.Trp384Arg
NP_001340884.1:p.Trp384Arg
NP_001340886.1:p.Trp384Arg
NP_001340887.1:p.Trp384Arg
NP_001340889.1:p.Trp384Arg
NP_008851.3:p.Trp384Arg
LRG_8:g.30993T>A
NC_000002.11:g.166904157A>T
NM_001165963.1:c.1150T>A
NR_148667.2:n.1536T>A

Protein change:

W384R

Links:

dbSNP: rs1057523858

NCBI 1000 Genomes Browser:

rs1057523858

Molecular consequence:

NM_001353961.2:c.-1276T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.1150T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.1536T>A - 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
SCV000757869	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2017)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25348405, 18804930, 23195492, 21248271, 23762420, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000757869

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 22, 2017)

germline

clinical testing

PubMed (6)
[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

UniProt: a hub for protein information.

UniProt Consortium..

Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12. doi: 10.1093/nar/gku989. Epub 2014 Oct 27.

PubMed [citation]

PMID:: 25348405
PMCID:: PMC4384041

A catalog of SCN1A variants.

Lossin C.

Brain Dev. 2009 Feb;31(2):114-30. doi: 10.1016/j.braindev.2008.07.011. Epub 2008 Sep 19. Review. Erratum in: Brain Dev. 2014 Jan;36(1):90.

PubMed [citation]

PMID:: 18804930

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000757869.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces tryptophan with arginine at codon 384 of the SCN1A protein (p.Trp384Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant identified in the SCN1A gene is located in the extracellular D1-P1 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. For these reasons, this variant has been classified as Pathogenic. A different variant (c.1150T>C) giving rise to the same protein effect observed here (p.Trp384Arg) has been reported to be de novo in individuals affected with Dravet syndrome (PMID: 23195492, 21248271), indicating that this residue may be critical for protein function. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported to be de novo in an individual affected with Dravet Syndrome and vaccination induced seizures (PMID: 23762420). ClinVar contains an entry for this variant (Variation ID: 390676).

#	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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