NM_001330260.2(SCN8A):c.4948G>A (p.Ala1650Thr) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 10, 2016
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:: RCV000390676.9

Allele description [Variation Report for NM_001330260.2(SCN8A):c.4948G>A (p.Ala1650Thr)]

NM_001330260.2(SCN8A):c.4948G>A (p.Ala1650Thr)

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.4948G>A (p.Ala1650Thr)

HGVS:

NC_000012.12:g.51806434G>A
NG_021180.3:g.221477G>A
NM_001177984.3:c.4825G>A
NM_001330260.2:c.4948G>AMANE SELECT
NM_001369788.1:c.4825G>A
NM_014191.4:c.4948G>A
NP_001171455.1:p.Ala1609Thr
NP_001317189.1:p.Ala1650Thr
NP_001356717.1:p.Ala1609Thr
NP_055006.1:p.Ala1650Thr
LRG_1389t1:c.4948G>A
LRG_1389t2:c.4948G>A
LRG_1389:g.221477G>A
LRG_1389p1:p.Ala1650Thr
LRG_1389p2:p.Ala1650Thr
NC_000012.11:g.52200218G>A
NM_014191.3:c.4948G>A
Q9UQD0:p.Ala1650Thr

Protein change:

A1609T

Links:

UniProtKB: Q9UQD0#VAR_071680; dbSNP: rs879255709

NCBI 1000 Genomes Browser:

rs879255709

Molecular consequence:

NM_001177984.3:c.4825G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.4948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.4825G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.4948G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Chain 7, V-type proton ATPase 16 kDa proteolipid subunit
Chain 7, V-type proton ATPase 16 kDa proteolipid subunit
gi|1950844017|pdb|6WLW|7

Protein

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
SCV000329746	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Feb 10, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329746

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Feb 10, 2016)

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, SCV000329746.6

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

Description

The A1650T pathogenic variant in the SCN8A gene has been reported previously as a de novo variant in two unrelated individuals whose combined features include intractable early-onset epileptic encephalopathy, severely regressed development, intellectual disability, quadriparesis with dystonic posturing, hypotonia, and MRI abnormalities including asymmetric ventricles and mild diffuse atrophy (Larsen et al., 2015; Ohba et al., 2014). The A1650T variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A1650T 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. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A1650T 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: Oct 13, 2024

ClinVar

Relating variation to medicine