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NM_139058.3(ARX):c.1125G>A (p.Trp375Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 4, 2020
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:
RCV001883211.4

Allele description [Variation Report for NM_139058.3(ARX):c.1125G>A (p.Trp375Ter)]

NM_139058.3(ARX):c.1125G>A (p.Trp375Ter)

Gene:
ARX:aristaless related homeobox [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp21.3
Genomic location:
Preferred name:
NM_139058.3(ARX):c.1125G>A (p.Trp375Ter)
HGVS:
  • NC_000023.11:g.25007434C>T
  • NG_008281.1:g.13515G>A
  • NM_139058.3:c.1125G>AMANE SELECT
  • NP_620689.1:p.Trp375Ter
  • NC_000023.10:g.25025551C>T
Protein change:
W375*
Links:
dbSNP: rs2147320638
NCBI 1000 Genomes Browser:
rs2147320638
Molecular consequence:
  • NM_139058.3:c.1125G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 1 (DEE1)
Synonyms:
INFANTILE SPASM SYNDROME, X-LINKED 1; X-linked infantile spasms; West's syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010632; MedGen: C3463992; OMIM: 308350
Name:
Intellectual disability, X-linked, with or without seizures, arx-related (XLID29)
Synonyms:
MENTAL RETARDATION, X-LINKED 29; MENTAL RETARDATION, X-LINKED 32; MENTAL RETARDATION, X-LINKED 33; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010317; MedGen: C0796244; Orphanet: 777; OMIM: 300419

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002142115Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 4, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females.

Marsh E, Fulp C, Gomez E, Nasrallah I, Minarcik J, Sudi J, Christian SL, Mancini G, Labosky P, Dobyns W, Brooks-Kayal A, Golden JA.

Brain. 2009 Jun;132(Pt 6):1563-76. doi: 10.1093/brain/awp107. Epub 2009 May 12.

PubMed [citation]
PMID:
19439424
PMCID:
PMC2685924

Ohtahara syndrome in a family with an ARX protein truncation mutation (c.81C>G/p.Y27X).

Fullston T, Brueton L, Willis T, Philip S, MacPherson L, Finnis M, Gecz J, Morton J.

Eur J Hum Genet. 2010 Feb;18(2):157-62. doi: 10.1038/ejhg.2009.139. Epub 2009 Sep 9.

PubMed [citation]
PMID:
19738637
PMCID:
PMC2987188
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002142115.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Trp375*) in the ARX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARX are known to be pathogenic (PMID: 19439424, 19738637). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with ARX-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024