NM_001330260.2(SCN8A):c.4850G>A (p.Arg1617Gln) AND Developmental and epileptic encephalopathy, 13

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jul 14, 2016
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:: RCV000144154.17

Allele description [Variation Report for NM_001330260.2(SCN8A):c.4850G>A (p.Arg1617Gln)]

NM_001330260.2(SCN8A):c.4850G>A (p.Arg1617Gln)

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_001330260.2(SCN8A):c.4850G>A (p.Arg1617Gln)

HGVS:

NC_000012.12:g.51806336G>A
NG_021180.3:g.221379G>A
NM_001177984.3:c.4727G>A
NM_001330260.2:c.4850G>AMANE SELECT
NM_001369788.1:c.4727G>A
NM_014191.4:c.4850G>A
NP_001171455.1:p.Arg1576Gln
NP_001317189.1:p.Arg1617Gln
NP_001356717.1:p.Arg1576Gln
NP_055006.1:p.Arg1617Gln
LRG_1389t1:c.4850G>A
LRG_1389t2:c.4850G>A
LRG_1389:g.221379G>A
LRG_1389p1:p.Arg1617Gln
LRG_1389p2:p.Arg1617Gln
NC_000012.11:g.52200120G>A
NM_014191.2:c.4850G>A
NM_014191.3:c.4850G>A
Q9UQD0:p.Arg1617Gln

Protein change:

R1576Q; ARG1617GLN

Links:

UniProtKB: Q9UQD0#VAR_071679; OMIM: 600702.0004; dbSNP: rs587777721

NCBI 1000 Genomes Browser:

rs587777721

Molecular consequence:

NM_001177984.3:c.4727G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.4727G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Acceleration of recovery from fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0053]
Increase in resurgent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0099]
Increase in slope of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0073]
Normal peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0096]
Normal slope of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0036]
Normal voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0032]
Normal voltage dependence of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0070]
Overall gain-of-function effect with respect to biophysical channel activity [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0140]
Severe increase in persistent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0043]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 13 (DEE13)
Synonyms:: Early infantile epileptic encephalopathy 13; SCN8A-Related Epilepsy
Identifiers:: MONDO: MONDO:0013801; MedGen: C3281191; Orphanet: 442835; OMIM: 614558

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189234	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000297794	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha	criteria provided, single submitter (HA_assertions_20161101)	Pathogenic (Jul 14, 2016)	de novo	research	Citation Link,
SCV000298208	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (5) [See all records that cite these PMIDs] 25046240, 26235739, 25568300, 24888894, 23020937

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000189234

OMIM

no assertion criteria provided

Pathogenic
(Jul 1, 2014)

germline

literature only

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

SCV000297794

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha

criteria provided, single submitter

(HA_assertions_20161101)

Pathogenic
(Jul 14, 2016)

de novo

research

Citation Link,

SCV000298208

GeneReviews

no classification provided

not provided

germline

literature only

PubMed (5)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	de novo	yes	1	not provided	not provided	1	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study.

Dyment DA, Tétreault M, Beaulieu CL, Hartley T, Ferreira P, Chardon JW, Marcadier J, Sawyer SL, Mosca SJ, Innes AM, Parboosingh JS, Bulman DE, Schwartzentruber J, Majewski J, Tarnopolsky M, Boycott KM; FORGE Canada Consortium.; Care4Rare Canada..

Clin Genet. 2015 Jul;88(1):34-40. doi: 10.1111/cge.12464. Epub 2014 Aug 28.

PubMed [citation]

PMID:: 25046240

In response: SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability.

Kong W, Zhang Y, Jiang Y.

Epilepsia. 2015 Aug;56(8):1320. doi: 10.1111/epi.13059. No abstract available.

PubMed [citation]

PMID:: 26235739

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000189234.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 2-year-old Japanese girl (patient 4) with developmental and epileptic encephalopathy-13 (DEE13; 614558), Ohba et al. (2014) identified a de novo heterozygous c.4850G-A transition in the SCN8A gene, resulting in an arg1617-to-gln (R1617Q) substitution at a highly conserved residue in the S4 transmembrane segment that plays a role in voltage sensing. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Sequencing Project database or in 408 in-house control exomes. Functional studies of the variant were not performed. The patient had onset of seizures at 3 months of age.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha, SCV000297794.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	1	not provided	not provided		1	not provided	not provided	not provided

From GeneReviews, SCV000298208.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (5)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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