NM_139058.3(ARX):c.1270C>G (p.Pro424Ala) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 17, 2022
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:: RCV002009436.4

Allele description [Variation Report for NM_139058.3(ARX):c.1270C>G (p.Pro424Ala)]

NM_139058.3(ARX):c.1270C>G (p.Pro424Ala)

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.1270C>G (p.Pro424Ala)

HGVS:

NC_000023.11:g.25007289G>C
NG_008281.1:g.13660C>G
NM_139058.3:c.1270C>GMANE SELECT
NP_620689.1:p.Pro424Ala
NC_000023.10:g.25025406G>C

Protein change:

P424A

Links:

dbSNP: rs2147320496

NCBI 1000 Genomes Browser:

rs2147320496

Molecular consequence:

NM_139058.3:c.1270C>G - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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OR2AK2 olfactory receptor family 2 subfamily AK member 2 [Homo sapiens]
OR2AK2 olfactory receptor family 2 subfamily AK member 2 [Homo sapiens]
Gene ID:391191

Gene
OR2AK1P AND (alive[prop]) (1)
Gene
Homo sapiens phosphoglycerate kinase 2 (PGK2), mRNA
Homo sapiens phosphoglycerate kinase 2 (PGK2), mRNA
gi|1653962345|ref|NM_138733.5|

Nucleotide
Homo sapiens EPH receptor A2 (EPHA2), RefSeqGene on chromosome 1
Homo sapiens EPH receptor A2 (EPHA2), RefSeqGene on chromosome 1
gi|297374761|ref|NG_021396.1|

Nucleotide
JGI_CABH7476.rev NIH_XGC_tropSkeMus1 Xenopus tropicalis cDNA clone IMAGE:7850567...
JGI_CABH7476.rev NIH_XGC_tropSkeMus1 Xenopus tropicalis cDNA clone IMAGE:7850567 3', mRNA sequence
gi|73775220|gnl|dbEST|31030435|gb|D 23.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002289156	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002289156

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 17, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002289156.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARX protein function. This variant has not been reported in the literature in individuals affected with ARX-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 424 of the ARX protein (p.Pro424Ala).

#	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 8, 2024

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