NM_001330260.2(SCN8A):c.5615G>A (p.Arg1872Gln) AND Developmental and epileptic encephalopathy, 13

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 28, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000239745.12

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5615G>A (p.Arg1872Gln)]

NM_001330260.2(SCN8A):c.5615G>A (p.Arg1872Gln)

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.5615G>A (p.Arg1872Gln)

Other names:

NM_001330260.2(SCN8A):c.5615G>A

HGVS:

NC_000012.12:g.51807101G>A
NG_021180.3:g.222144G>A
NM_001177984.3:c.5492G>A
NM_001330260.2:c.5615G>AMANE SELECT
NM_001369788.1:c.5492G>A
NM_014191.4:c.5615G>A
NP_001171455.1:p.Arg1831Gln
NP_001317189.1:p.Arg1872Gln
NP_001356717.1:p.Arg1831Gln
NP_055006.1:p.Arg1872Gln
LRG_1389t1:c.5615G>A
LRG_1389t2:c.5615G>A
LRG_1389:g.222144G>A
LRG_1389p1:p.Arg1872Gln
LRG_1389p2:p.Arg1872Gln
NC_000012.11:g.52200885G>A
NM_001330260.1:c.5615G>A
NM_014191.3:c.5615G>A
Q9UQD0:p.Arg1872Gln

Protein change:

R1831Q

Links:

UniProtKB: Q9UQD0#VAR_076616; dbSNP: rs796053229

NCBI 1000 Genomes Browser:

rs796053229

Molecular consequence:

NM_001177984.3:c.5492G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.5615G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.5492G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.5615G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Decrease in slope of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0034]
Mild depolarizing shift of voltage dependence of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0062]
Mild hyperpolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0029]
Moderate increase in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0094]
Normal persistent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0044]
Normal rate of recovery from fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0054]
Normal resurgent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0100]
Normal slope of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0074]
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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000298216	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001522182	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 24, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002059441	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000298216

GeneReviews

no classification provided

not provided

germline

literature only

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

SCV001522182

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 24, 2019)

unknown

clinical testing

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

SCV002059441

Centogene AG - the Rare Disease Company

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 28, 2021)

germline

clinical testing

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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The phenotypic spectrum of SCN8A encephalopathy.

Larsen J, Carvill GL, Gardella E, Kluger G, Schmiedel G, Barisic N, Depienne C, Brilstra E, Mang Y, Nielsen JE, Kirkpatrick M, Goudie D, Goldman R, Jähn JA, Jepsen B, Gill D, Döcker M, Biskup S, McMahon JM, Koeleman B, Harris M, Braun K, et al.

Neurology. 2015 Feb 3;84(5):480-9. doi: 10.1212/WNL.0000000000001211. Epub 2015 Jan 7.

PubMed [citation]

PMID:: 25568300
PMCID:: PMC4336074

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

Details of each submission

From GeneReviews, SCV000298216.2

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

#	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

From Baylor Genetics, SCV001522182.1

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

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

#	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 Centogene AG - the Rare Disease Company, SCV002059441.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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