NM_001330260.2(SCN8A):c.5630A>G (p.Asn1877Ser) AND Developmental and epileptic encephalopathy, 13

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: May 28, 2019
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:: RCV000239630.7

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5630A>G (p.Asn1877Ser)]

NM_001330260.2(SCN8A):c.5630A>G (p.Asn1877Ser)

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.5630A>G (p.Asn1877Ser)

Other names:

p.N1877S:AAT>AGT

HGVS:

NC_000012.12:g.51807116A>G
NG_021180.3:g.222159A>G
NM_001177984.3:c.5507A>G
NM_001330260.2:c.5630A>GMANE SELECT
NM_001369788.1:c.5507A>G
NM_014191.4:c.5630A>G
NP_001171455.1:p.Asn1836Ser
NP_001317189.1:p.Asn1877Ser
NP_001356717.1:p.Asn1836Ser
NP_055006.1:p.Asn1877Ser
LRG_1389t1:c.5630A>G
LRG_1389t2:c.5630A>G
LRG_1389:g.222159A>G
LRG_1389p1:p.Asn1877Ser
LRG_1389p2:p.Asn1877Ser
NC_000012.11:g.52200900A>G
NM_001330260.2:c.5630A>G
NM_014191.3:c.5630A>G
Q9UQD0:p.Asn1877Ser

Protein change:

N1836S; ASN1877SER

Links:

UniProtKB: Q9UQD0#VAR_076617; OMIM: 600702.0011; dbSNP: rs587780455

NCBI 1000 Genomes Browser:

rs587780455

Molecular consequence:

NM_001177984.3:c.5507A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.5630A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.5507A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.5630A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Mild depolarizing shift of voltage dependence of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0062]
Normal fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0047]
Normal peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0096]
Normal rate of recovery from fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0054]
Normal slope of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0074]
Normal voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0032]
Overall gain-of-function effect with respect to biophysical channel activity [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0140]

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

Recent activity

Clear Turn Off Turn On

Homo sapiens secernin 1 (SCRN1), transcript variant 2, mRNA
Homo sapiens secernin 1 (SCRN1), transcript variant 2, mRNA
gi|1519244517|ref|NM_014766.5|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001138743	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001428375	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	no assertion criteria provided	Likely pathogenic (Jan 1, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001438355	OMIM	no assertion criteria provided	Pathogenic (Oct 19, 2020)	unknown	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001138743

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV001428375

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

no assertion criteria provided

Likely pathogenic
(Jan 1, 2019)

unknown

clinical testing

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

SCV001438355

OMIM

no assertion criteria provided

Pathogenic
(Oct 19, 2020)

unknown

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Autosomal dominant SCN8A mutation with an unusually mild phenotype.

Anand G, Collett-White F, Orsini A, Thomas S, Jayapal S, Trump N, Zaiwalla Z, Jayawant S.

Eur J Paediatr Neurol. 2016 Sep;20(5):761-5. doi: 10.1016/j.ejpn.2016.04.015. Epub 2016 Apr 30.

PubMed [citation]

PMID:: 27210545

Details of each submission

From Mendelics, SCV001138743.1

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

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

From Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille, SCV001428375.1

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

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

From OMIM, SCV001438355.1

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

Description

In a father and son with benign familial infantile seizures-5 (BFIS5; 617080), Anand et al. (2016) identified a heterozygous c.5630A-G transition (c.5630A-G, NM_014191.3) in the SCN8A gene, resulting in an asn1877-to-ser (N1877S) substitution in a conserved region that contains binding sites for interacting proteins. The mutation, which was found by next generation sequence analysis, was not present in the dbSNP, 1000 Genomes Project, or the Exome Variant Server databases. The authors stated that the same variant had been described by several laboratories, including ClinVar (SCV000152660.1) and GeneDx (SCV000242923.2), in patients with epilepsy, developmental delay, and intellectual disability, consistent with developmental and epileptic encephalopathy-13 (DEE13; 614558). Functional studies of the variant were not performed by Anand et al. (2016). The benign phenotype in the father and son suggested that they may carry additional variants in other genes that offer a protective effect. Sanger sequencing of the father did not show somatic mosaicism for the SCN8A mutation.

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

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine