NM_152296.5(ATP1A3):c.2839G>C (p.Gly947Arg) AND Dystonia 12

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 16, 2021
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:: RCV001849915.16

Allele description [Variation Report for NM_152296.5(ATP1A3):c.2839G>C (p.Gly947Arg)]

NM_152296.5(ATP1A3):c.2839G>C (p.Gly947Arg)

Gene:

ATP1A3:ATPase Na+/K+ transporting subunit alpha 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_152296.5(ATP1A3):c.2839G>C (p.Gly947Arg)

Other names:

ATP1A3, NT2839G-C, GLY947ARG

HGVS:

NC_000019.10:g.41967744C>G
NG_008015.1:g.31487G>C
NM_001256213.2:c.2872G>C
NM_001256214.2:c.2878G>C
NM_152296.5:c.2839G>CMANE SELECT
NP_001243142.1:p.Gly958Arg
NP_001243143.1:p.Gly960Arg
NP_689509.1:p.Gly947Arg
NP_689509.1:p.Gly947Arg
LRG_1186t1:c.2839G>C
LRG_1186:g.31487G>C
LRG_1186p1:p.Gly947Arg
NC_000019.9:g.42471896C>G
NM_152296.3:c.2839G>C
NM_152296.4:c.2839G>C
P13637:p.Gly947Arg

Protein change:

G947R; GLY947ARG

Links:

UniProtKB: P13637#VAR_068950; OMIM: 182350.0013; dbSNP: rs398122887

NCBI 1000 Genomes Browser:

rs398122887

Molecular consequence:

NM_001256213.2:c.2872G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001256214.2:c.2878G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_152296.5:c.2839G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dystonia 12 (DYT12)
Synonyms:: DYT-ATP1A3; Rapid-Onset Dystonia-Parkinsonism
Identifiers:: MONDO: MONDO:0007496; MedGen: C1868681; Orphanet: 71517; OMIM: 128235

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000195726	GeneReviews	no classification provided	not provided	germline	literature only
SCV002232575	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 16, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24631656, 22842232, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000195726

GeneReviews

no classification provided

not provided

germline

literature only

SCV002232575

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 16, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only

Citations

PubMed

Alternating Hemiplegia of Childhood mutations have a differential effect on Na(+),K(+)-ATPase activity and ouabain binding.

Weigand KM, Messchaert M, Swarts HG, Russel FG, Koenderink JB.

Biochim Biophys Acta. 2014 Jul;1842(7):1010-6. doi: 10.1016/j.bbadis.2014.03.002. Epub 2014 Mar 12.

PubMed [citation]

PMID:: 24631656

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood.

Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, Tiziano FD, Fontaine B, Walley NM, Heavin S, Panagiotakaki E; European Alternating Hemiplegia of Childhood (AHC) Genetics Consortium.; Biobanca e Registro Clinico per l'Emiplegia Alternante (I.B.AHC) Consortium.; European Network for Research on Alternating Hemiplegia (ENRAH) for Small and Medium-sized Enterpriese (SMEs) Consortium., Fiori S, Abiusi E, Di Pietro L, Sweney MT, Newcomb TM, Viollet L, Huff C, Jorde LB, et al.

Nat Genet. 2012 Sep;44(9):1030-4. doi: 10.1038/ng.2358. Epub 2012 Jul 29.

PubMed [citation]

PMID:: 22842232
PMCID:: PMC3442240

See all PubMed Citations (3)

Details of each submission

From GeneReviews, SCV000195726.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002232575.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 947 of the ATP1A3 protein (p.Gly947Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant has been reported to affect ATP1A3 protein function (PMID: 24631656). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly947 amino acid residue in ATP1A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This missense change has been observed in individual(s) with alternating hemiplegia of childhood (PMID: 22842232). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 139579).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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