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NM_139058.3(ARX):c.1226C>A (p.Pro409Gln) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 15, 2018
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:
RCV000799400.7

Allele description [Variation Report for NM_139058.3(ARX):c.1226C>A (p.Pro409Gln)]

NM_139058.3(ARX):c.1226C>A (p.Pro409Gln)

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.1226C>A (p.Pro409Gln)
HGVS:
  • NC_000023.11:g.25007333G>T
  • NG_008281.1:g.13616C>A
  • NM_139058.3:c.1226C>AMANE SELECT
  • NP_620689.1:p.Pro409Gln
  • NC_000023.10:g.25025450G>T
  • NM_139058.2:c.1226C>A
Protein change:
P409Q
Links:
dbSNP: rs1601946603
NCBI 1000 Genomes Browser:
rs1601946603
Molecular consequence:
  • NM_139058.3:c.1226C>A - 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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000939060Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 15, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV000939060.4

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

Description

This variant has not been reported in the literature in individuals with ARX-related disease. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This sequence change replaces proline with glutamine at codon 409 of the ARX protein (p.Pro409Gln). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and glutamine.

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

Last Updated: Oct 8, 2024