NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 11, 2023
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:: RCV000456891.17

Allele description [Variation Report for NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)]

NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)

Genes:

LOC109610631:aristaless related homeobox polyalanine expansion region [Gene]
ARX:aristaless related homeobox [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

Xp21.3

Genomic location:

Preferred name:

NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)

Other names:

NP_620689.1:p.(Ala109_Ala115dup)

HGVS:

NC_000023.11:g.25013662CGC[17]
NG_008281.1:g.7260GGC[17]
NG_052655.1:g.233CGC[17]
NM_139058.3:c.306GGC[17]MANE SELECT
NP_620689.1:p.Ala109_Ala115dup
NC_000023.10:g.25031776_25031777insGCCGCCGCCGCCGCCGCCGCC
NC_000023.10:g.25031779CGC[17]
NM_139058.2:c.315_335dupGGCGGCGGCGGCGGCGGCGGC
NM_139058.3:c.315_335dupMANE SELECT

Links:

OMIM: 300382.0001; dbSNP: rs387906492

NCBI 1000 Genomes Browser:

rs387906492

Molecular consequence:

NM_139058.3:c.306GGC[17] - inframe_insertion - [Sequence Ontology: SO:0001821]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551640	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11889467, 15726411, 17664401, 26029707, 17490853, 23246292, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551640

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 11, 2023)

germline

clinical testing

PubMed (7)
[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

Citations

PubMed

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy.

Strømme P, Mangelsdorf ME, Shaw MA, Lower KM, Lewis SM, Bruyere H, Lütcherath V, Gedeon AK, Wallace RH, Scheffer IE, Turner G, Partington M, Frints SG, Fryns JP, Sutherland GR, Mulley JC, Gécz J.

Nat Genet. 2002 Apr;30(4):441-5. Epub 2002 Mar 11.

PubMed [citation]

PMID:: 11889467

Familial West syndrome and dystonia caused by an Aristaless related homeobox gene mutation.

Wohlrab G, Uyanik G, Gross C, Hehr U, Winkler J, Schmitt B, Boltshauser E.

Eur J Pediatr. 2005 May;164(5):326-8. Epub 2005 Feb 22. No abstract available.

PubMed [citation]

PMID:: 15726411

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000551640.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This variant, c.315_335dup, results in the insertion of 7 amino acid(s) of the ARX protein (p.Ala109_Ala115dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has been observed in individual(s) with early-onset epilepsy (PMID: 11889467, 15726411, 17664401, 26029707). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as c.333_334ins(GCG)7 and (GCG)10+7. ClinVar contains an entry for this variant (Variation ID: 11186). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ARX function (PMID: 17490853, 23246292). For these reasons, this variant has been classified as Pathogenic.

#	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: Nov 10, 2024

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