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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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000757869Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 22, 2017)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024