NM_001165963.4(SCN1A):c.2791C>T (p.Arg931Cys) AND Early infantile epileptic encephalopathy with suppression bursts

Clinical significance:Pathogenic (Last evaluated: Jun 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000636409.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.2791C>T (p.Arg931Cys)]

NM_001165963.4(SCN1A):c.2791C>T (p.Arg931Cys)

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.2791C>T (p.Arg931Cys)
Other names:
p.R931C:CGC>TGC
HGVS:
  • NC_000002.12:g.166037931G>A
  • NG_011906.1:g.40709C>T
  • NM_001165963.4:c.2791C>TMANE SELECT
  • NM_001165964.3:c.2707C>T
  • NM_001202435.3:c.2791C>T
  • NM_001353948.2:c.2791C>T
  • NM_001353949.2:c.2758C>T
  • NM_001353950.2:c.2758C>T
  • NM_001353951.2:c.2758C>T
  • NM_001353952.2:c.2758C>T
  • NM_001353954.2:c.2755C>T
  • NM_001353955.2:c.2755C>T
  • NM_001353957.2:c.2707C>T
  • NM_001353958.2:c.2707C>T
  • NM_001353960.2:c.2704C>T
  • NM_001353961.2:c.349C>T
  • NM_006920.6:c.2758C>T
  • NP_001159435.1:p.Arg931Cys
  • NP_001159435.1:p.Arg931Cys
  • NP_001159436.1:p.Arg903Cys
  • NP_001189364.1:p.Arg931Cys
  • NP_001340877.1:p.Arg931Cys
  • NP_001340878.1:p.Arg920Cys
  • NP_001340879.1:p.Arg920Cys
  • NP_001340880.1:p.Arg920Cys
  • NP_001340881.1:p.Arg920Cys
  • NP_001340883.1:p.Arg919Cys
  • NP_001340884.1:p.Arg919Cys
  • NP_001340886.1:p.Arg903Cys
  • NP_001340887.1:p.Arg903Cys
  • NP_001340889.1:p.Arg902Cys
  • NP_001340890.1:p.Arg117Cys
  • NP_008851.3:p.Arg920Cys
  • LRG_8t1:c.2758C>T
  • LRG_8:g.40709C>T
  • NC_000002.11:g.166894441G>A
  • NM_001165963.1:c.2791C>T
  • NM_006920.4:c.2758C>T
  • NR_148667.2:n.3144C>T
  • AF225985.1:c.2761C>T
Protein change:
R117C; Arg921Cys
Links:
UniProtKB/Swiss-Prot: VAR_029678; dbSNP: rs121918788
NCBI 1000 Genomes Browser:
rs121918788
Molecular consequence:
  • NM_001165963.4:c.2791C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.2707C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.2791C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.2791C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.2758C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.2758C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.2758C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.2758C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.2755C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.2755C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.2707C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.2707C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.2704C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.349C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.2758C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.3144C>T - 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
SCV000757848Invitaecriteria provided, single submitter
Pathogenic
(Jun 21, 2020)
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

Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy.

Ohmori I, Ouchida M, Ohtsuka Y, Oka E, Shimizu K.

Biochem Biophys Res Commun. 2002 Jul 5;295(1):17-23.

PubMed [citation]
PMID:
12083760

A screening test for the prediction of Dravet syndrome before one year of age.

Hattori J, Ouchida M, Ono J, Miyake S, Maniwa S, Mimaki N, Ohtsuka Y, Ohmori I.

Epilepsia. 2008 Apr;49(4):626-33. Epub 2007 Dec 11.

PubMed [citation]
PMID:
18076640
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000757848.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine with cysteine at codon 931 of the SCN1A protein (p.Arg931Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with Dravet syndrome (PMID: 12083760, 18076640). This variant is also known as Arg921Cys in the literature. ClinVar contains an entry for this variant (Variation ID: 68598). 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 disrupts the p.Arg931 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25243660, 27231140, 28079314). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 24, 2021

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