U.S. flag

An official website of the United States government

NM_001330260.2(SCN8A):c.5614C>T (p.Arg1872Trp) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 11, 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:
RCV000189289.12

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5614C>T (p.Arg1872Trp)]

NM_001330260.2(SCN8A):c.5614C>T (p.Arg1872Trp)

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.5614C>T (p.Arg1872Trp)
HGVS:
  • NC_000012.12:g.51807100C>T
  • NG_021180.3:g.222143C>T
  • NM_001177984.3:c.5491C>T
  • NM_001330260.2:c.5614C>TMANE SELECT
  • NM_001369788.1:c.5491C>T
  • NM_014191.4:c.5614C>T
  • NP_001171455.1:p.Arg1831Trp
  • NP_001317189.1:p.Arg1872Trp
  • NP_001356717.1:p.Arg1831Trp
  • NP_055006.1:p.Arg1872Trp
  • NP_055006.1:p.Arg1872Trp
  • LRG_1389t1:c.5614C>T
  • LRG_1389t2:c.5614C>T
  • LRG_1389:g.222143C>T
  • LRG_1389p1:p.Arg1872Trp
  • LRG_1389p2:p.Arg1872Trp
  • NC_000012.11:g.52200884C>T
  • NM_014191.2:c.5614C>T
  • NM_014191.3:c.5614C>T
  • Q9UQD0:p.Arg1872Trp
  • p.R1872W
Protein change:
R1831W
Links:
UniProtKB: Q9UQD0#VAR_071681; dbSNP: rs796053228
NCBI 1000 Genomes Browser:
rs796053228
Molecular consequence:
  • NM_001177984.3:c.5491C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330260.2:c.5614C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369788.1:c.5491C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014191.4:c.5614C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
  • Increase in persistent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0040]
  • 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]
  • Overall gain-of-function effect with respect to biophysical channel activity [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0140]
  • Slowing of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0048]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000242921GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Pathogenic
(Apr 11, 2019) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000242921.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Published functional studies demonstrate R1872W impaired the sodium channel transition from open state to inactivated state, resulting in channel hyperactivity (Wagnon et al., 2016); Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32139178, 32090326, 31402610, 31026061, 30615093, 30171078, 30601941, 27779742, 29852413, 26900580, 25951352, 24888894)

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

Last Updated: Sep 8, 2024