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NM_152296.5(ATP1A3):c.2452G>A (p.Glu818Lys)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
10 (Most recent: Oct 9, 2021)
Last evaluated:
Oct 1, 2021
Accession:
VCV000156238.16
Variation ID:
156238
Description:
single nucleotide variant
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NM_152296.5(ATP1A3):c.2452G>A (p.Glu818Lys)

Allele ID
166024
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19q13.2
Genomic location
19: 41970275 (GRCh38) GRCh38 UCSC
19: 42474427 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.9:g.42474427C>T
LRG_1186:g.28956G>A
LRG_1186t1:c.2452G>A LRG_1186p1:p.Glu818Lys
... more HGVS
Protein change
E818K, E829K, E831K
Other names
-
Canonical SPDI
NC_000019.10:41970274:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA204733
UniProtKB: P13637#VAR_070772
OMIM: 182350.0014
dbSNP: rs587777771
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 criteria provided, multiple submitters, no conflicts Oct 1, 2021 RCV000144250.9
Pathogenic 2 criteria provided, multiple submitters, no conflicts Dec 15, 2020 RCV000314245.5
Pathogenic 1 criteria provided, single submitter Aug 29, 2014 RCV000190725.4
Pathogenic 1 criteria provided, single submitter Jul 20, 2015 RCV000195001.2
Pathogenic 1 criteria provided, single submitter Jan 28, 2020 RCV000234480.4

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ATP1A3 - - GRCh38
GRCh37
604 618

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jul 20, 2015)
criteria provided, single submitter
Method: clinical testing
Alternating hemiplegia of childhood 2
Allele origin: germline
Genetic Services Laboratory,University of Chicago
Accession: SCV000246633.1
Submitted: (Sep 15, 2015)
Evidence details
Pathogenic
(Aug 29, 2014)
criteria provided, single submitter
Method: clinical testing
Inborn genetic diseases
Allele origin: germline
Ambry Genetics
Accession: SCV000244166.6
Submitted: (Oct 09, 2020)
Evidence details
Pathogenic
(Jan 28, 2020)
criteria provided, single submitter
Method: clinical testing
Dystonia 12
Allele origin: germline
Invitae
Accession: SCV000291489.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces glutamic acid with lysine at codon 818 of the ATP1A3 protein (p.Glu818Lys). The glutamic acid residue is moderately conserved and there … (more)
Pathogenic
(Dec 15, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000329953.5
Submitted: (Sep 24, 2021)
Evidence details
Comment:
Published functional studies demonstrate a damaging effect with reduced pump turnover rate and failure to rapidly regain the resting membrane potential following action potentials (Roenn … (more)
Pathogenic
(Jul 15, 2019)
criteria provided, single submitter
Method: clinical testing
Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
Allele origin: de novo
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001429018.1
Submitted: (Apr 20, 2020)
Evidence details
Comment:
This variant was identified as de novo (maternity and paternity confirmed).
Pathogenic
(Mar 01, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001247063.6
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(Oct 01, 2021)
criteria provided, single submitter
Method: clinical testing
Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
Allele origin: paternal
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV001976671.1
Submitted: (Oct 09, 2021)
Evidence details
Publications
PubMed (1)
Comment:
PM1, PM2, PP3, PP5
Pathogenic
(May 04, 2014)
no assertion criteria provided
Method: literature only
Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorinural hearing loss
Allele origin: de novo
GeneReviews
Accession: SCV000195717.1
Submitted: (Nov 06, 2014)
Evidence details
Other databases
http://www.ncbi.nlm.nih.gov/book…
Pathogenic
(Aug 26, 2014)
no assertion criteria provided
Method: literature only
CEREBELLAR ATAXIA, AREFLEXIA, PES CAVUS, OPTIC ATROPHY, AND SENSORINEURAL HEARING LOSS
Allele origin: germline
OMIM
Accession: SCV000189408.4
Submitted: (Sep 29, 2014)
Evidence details
Publications
PubMed (4)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
Allele origin: germline
Genomics England Pilot Project,Genomics England
Accession: SCV001760451.1
Submitted: (Jul 15, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders. Marinakis NM American journal of medical genetics. Part A 2021 PMID: 34008892
The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management. Tranebjærg L Human genetics 2018 PMID: 29305691
<i>ATP1A3-</i>Related Neurologic Disorders Brashear A - 2018 PMID: 20301294
CAPOS syndrome and hemiplegic migraine in a novel pedigree with the specific ATP1A3 mutation. Potic A Journal of the neurological sciences 2015 PMID: 26453127
CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss: A Third Allelic Disorder of the ATP1A3 Gene. Heimer G Journal of child neurology 2015 PMID: 25895915
Phenotypic overlap of alternating hemiplegia of childhood and CAPOS syndrome. Rosewich H Neurology 2014 PMID: 25056583
A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Demos MK Orphanet journal of rare diseases 2014 PMID: 24468074
Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome. Nicolaides P Journal of medical genetics 1996 PMID: 8733056
http://www.ncbi.nlm.nih.gov/books/NBK1115/ - - - -

Text-mined citations for rs587777771...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 20, 2021