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NM_003924.4(PHOX2B):c.446G>T (p.Arg149Leu) AND Congenital central hypoventilation

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 26, 2021
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001078157.4

Allele description [Variation Report for NM_003924.4(PHOX2B):c.446G>T (p.Arg149Leu)]

NM_003924.4(PHOX2B):c.446G>T (p.Arg149Leu)

Gene:
PHOX2B:paired like homeobox 2B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p13
Genomic location:
Preferred name:
NM_003924.4(PHOX2B):c.446G>T (p.Arg149Leu)
HGVS:
  • NC_000004.12:g.41746306C>A
  • NG_008243.1:g.7665G>T
  • NM_003924.4:c.446G>TMANE SELECT
  • NP_003915.2:p.Arg149Leu
  • LRG_513t1:c.446G>T
  • LRG_513:g.7665G>T
  • NC_000004.11:g.41748323C>A
  • NM_003924.3:c.446G>T
Protein change:
R149L; ARG149LEU
Links:
OMIM: 603851.0010; dbSNP: rs1733899167
NCBI 1000 Genomes Browser:
rs1733899167
Molecular consequence:
  • NM_003924.4:c.446G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital central hypoventilation
Synonyms:
Idiopathic congenital central alveolar hypoventilation; Congenital failure of autonomic control; Primary alveolar hypoventilation; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0800031; MedGen: C1275808; Orphanet: 661; Orphanet: 99803; OMIM: PS209880

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001244208OMIM
no assertion criteria provided
Pathogenic
(Aug 26, 2021) 		germlineliterature only

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

Hamosh, A. Personal Communication. 2020. Baltimore, Md.

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Congenital heart disease and aortic arch variants associated with mutation in PHOX2B.

Lombardo RC, Porollo A, Cnota JF, Hopkin RJ.

Genet Med. 2018 Dec;20(12):1538-1543. doi: 10.1038/gim.2018.34. Epub 2018 Mar 15.

PubMed [citation]
PMID:
29543228

Details of each submission

From OMIM, SCV001244208.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In an African American female (P003) with central hypoventilation syndrome (CCHS1; 209880), Lombardo et al. (2018) identified a c.446G-T transversion in exon 3 of the PHOX2B gene, resulting in an arginine-to-leucine substitution at codon 149 (R149L) in the homeobox domain of the protein. This patient also had moderate secundum atrial septal defect (ASD) and a patent ductus arteriosus (PDA) that required surgical closure at age 5 years.

Hamosh (2020) noted that the A149L variant was absent from the gnomAD database on April 12, 2020.

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

Last Updated: May 7, 2024