NM_014191.3(SCN8A):c.2952C>G (p.Asn984Lys) AND Early infantile epileptic encephalopathy 13

Clinical significance:Pathogenic (Last evaluated: Feb 19, 2016)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000172909.4

Allele description

NM_014191.3(SCN8A):c.2952C>G (p.Asn984Lys)

Gene:
SCN8A:sodium voltage-gated channel alpha subunit 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_014191.3(SCN8A):c.2952C>G (p.Asn984Lys)
HGVS:
  • NC_000012.12:g.51768915C>G
  • NG_021180.2:g.182680C>G
  • NM_014191.3:c.2952C>G
  • NP_055006.1:p.Asn984Lys
  • NC_000012.11:g.52162699C>G
  • NM_014191.2:c.2952C>G
  • Q9UQD0:p.Asn984Lys
Protein change:
N984K; ASN984LYS
Links:
UniProtKB: Q9UQD0#VAR_076607; OMIM: 600702.0008; dbSNP: rs876657399
NCBI 1000 Genomes Browser:
rs876657399
Molecular consequence:
  • NM_014191.3:c.2952C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Early infantile epileptic encephalopathy 13 (EIEE13)
Synonyms:
SCN8A-Related Epilepsy
Identifiers:
MedGen: C3281191; Orphanet: 442835; OMIM: 614558

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000223891OMIMno assertion criteria providedPathogenic
(May 1, 2015)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000298197GeneReviewsno assertion criteria providedPathogenic
(Feb 19, 2016)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.

Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans MC, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels RJ, Meisler MH, Kamsteeg EJ.

J Med Genet. 2015 May;52(5):330-7. doi: 10.1136/jmedgenet-2014-102813. Epub 2015 Feb 27.

PubMed [citation]
PMID:
25725044
PMCID:
PMC4413743

Details of each submission

From OMIM, SCV000223891.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 7-year-old girl with early infantile epileptic encephalopathy-13 (EIEE13; 614558), Blanchard et al. (2015) identified a de novo heterozygous c.2952C-G transversion (c.2952C-G, NM_014191.2) in the SCN8A gene, resulting in an asn984-to-lys (N984K) substitution at a highly conserved residue adjacent to the transmembrane segment of the channel. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies in HEK293 cells showed that the mutation caused a 10-mV hyperpolarization shift, predicting premature channel opening and neuronal hyperactivity. The findings were consistent with a gain of function.

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

From GeneReviews, SCV000298197.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 24, 2018