NM_001330260.2(SCN8A):c.5615G>T (p.Arg1872Leu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 15, 2014
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:: RCV000189290.1

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5615G>T (p.Arg1872Leu)]

NM_001330260.2(SCN8A):c.5615G>T (p.Arg1872Leu)

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>T (p.Arg1872Leu)

HGVS:

NC_000012.12:g.51807101G>T
NG_021180.3:g.222144G>T
NM_001177984.3:c.5492G>T
NM_001330260.2:c.5615G>TMANE SELECT
NM_001369788.1:c.5492G>T
NM_014191.4:c.5615G>T
NP_001171455.1:p.Arg1831Leu
NP_001317189.1:p.Arg1872Leu
NP_001356717.1:p.Arg1831Leu
NP_055006.1:p.Arg1872Leu
LRG_1389t1:c.5615G>T
LRG_1389t2:c.5615G>T
LRG_1389:g.222144G>T
LRG_1389p1:p.Arg1872Leu
LRG_1389p2:p.Arg1872Leu
NC_000012.11:g.52200885G>T
NM_014191.3:c.5615G>T
Q9UQD0:p.Arg1872Leu
p.R1872L

Protein change:

R1831L

Links:

UniProtKB: Q9UQD0#VAR_076615; dbSNP: rs796053229

NCBI 1000 Genomes Browser:

rs796053229

Molecular consequence:

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

Functional consequence:

Mild decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0085]
Mild hyperpolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0029]
Mild increase in persistent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0041]
Normal slope of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0036]
Normal slope of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0074]
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]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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RecName: Full=MHC class II transactivator; Short=CIITA
RecName: Full=MHC class II transactivator; Short=CIITA
gi|317373472|sp|P33076.3|C2TA_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000242922	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Sep 15, 2014)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000242922

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Sep 15, 2014)

germline

clinical testing

Citation Link

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

Details of each submission

From GeneDx, SCV000242922.11

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

Description

p.Arg1872Leu (CGG>CTG): c.5615 G>T in exon 27 of the SCN8A gene (NM_014191.3)The R1872L mutation has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. R1872L is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a highly conserved position in the in the cytoplasmic domain after the 4th homologous repeat. In silico analysis predicts this substitution is probably damaging to the protein structure/function. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, it was previously identified at GeneDx as a de novo change in an individual with clinical features consistent with an SCN8A-related disorder. Although this mutation has not been reported previously to our knowledge, it is interpreted to be a disease-causing mutation. The variant is found in INFANT-EPI panel(s).

#	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: Sep 29, 2024

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