Submissions for variant NM_003924.4(PHOX2B):c.866dup (p.Pro290fs)

dbSNP: rs1733868277

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268540	SCV001447528	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224537	SCV003920313	pathogenic	Neuroblastoma, susceptibility to, 2; Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease	2021-03-30	criteria provided, single submitter	clinical testing	PHOX2B:NM_003924.3:exon3:c.866dupG:p.Pro290Serfs*70 DNA from this patient shows a heterozygous one nucleotide duplication in exon 3 that results in a frameshift (NM_003924.3: c.866dupG:p.Pro290Serfs*70). This variant is predicted to cause loss of normal protein function through protein truncation or nonsense mediated mRNA decay, and has not been reported in publicly available population databases of healthy individuals (including 1000 genomes, ExAC database and Exome Sequencing Project). Also, it has been reported in a patient with CCHS (Sasaki et al. Hum Genet. 2003 Dec;114(1):22-6.). Given its previous association with CCHS, absence from population databases and the clinical findings of this patient, this variant is classified as pathogenic. Heterozygous pathogenic variants in the PHOX2B gene are associated with CCHS[OMIM#209880].