NM_001330260.2(SCN8A):c.2890G>C (p.Gly964Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2018
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:: RCV000439821.2

Allele description [Variation Report for NM_001330260.2(SCN8A):c.2890G>C (p.Gly964Arg)]

NM_001330260.2(SCN8A):c.2890G>C (p.Gly964Arg)

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.2890G>C (p.Gly964Arg)

HGVS:

NC_000012.12:g.51766016G>C
NG_021180.3:g.181059G>C
NM_001177984.3:c.2890G>C
NM_001330260.2:c.2890G>CMANE SELECT
NM_001369788.1:c.2890G>C
NM_014191.4:c.2890G>C
NP_001171455.1:p.Gly964Arg
NP_001317189.1:p.Gly964Arg
NP_001356717.1:p.Gly964Arg
NP_055006.1:p.Gly964Arg
LRG_1389t1:c.2890G>C
LRG_1389t2:c.2890G>C
LRG_1389:g.181059G>C
LRG_1389p1:p.Gly964Arg
LRG_1389p2:p.Gly964Arg
NC_000012.11:g.52159800G>C
NM_014191.3:c.2890G>C

Protein change:

G964R; GLY964ARG

Links:

OMIM: 600702.0013; dbSNP: rs1057521662

NCBI 1000 Genomes Browser:

rs1057521662

Molecular consequence:

NM_001177984.3:c.2890G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.2890G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.2890G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.2890G>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Absence of peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0083]
Overall loss-of-function effect with respect to biophysical channel activity [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0144]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000523965	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jan 31, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000523965

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jan 31, 2018)

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, SCV000523965.4

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

Description

The G964R variant in the SCN8A gene has been previously reported as a de novo variant by whole exome sequencing in a child with global developmental delay, hypotonia, borderline intellectual disability, social communication disorder, and attention deficit hyperactivity disorder (Wagnon et al., 2017). The G964R variant is not observed in large population cohorts (Lek et al., 2016). The G964R variant 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. Functional studies of G964R transfected cells showed a complete loss of sodium channel activity (Wagnon et al., 2017). We interpret G964R as a pathogenic variant.

#	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: Apr 15, 2024

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