Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002445374 | SCV002733089 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-05-18 | criteria provided, single submitter | clinical testing | The p.Y78* pathogenic mutation (also known as c.234C>G), located in coding exon 1 of the PHOX2B gene, results from a C to G substitution at nucleotide position 234. This changes the amino acid from a tyrosine to a stop codon within coding exon 1. This mutation was maternally inherited in two siblings with Hirschsprung disease and respiratory issues; one sibling had several episodes of desaturations while the second sibling was diagnosed with central apnea. Their mother did not have Hirschsprung disease, but reported episodes of possible apneic episodes during sleep and awakening feeling breathless (Lombardo RC et al. Am. J. Med. Genet. A, 2017 Jun;173:1705-1709). This mutation has also been detected in an additional individual with hypopnea, intermittent desaturations, abnormal sleep study, and additional findings (Katwa U. Am. J. Med. Genet. A. 2018 07;176(7):1627-1631). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| OMIM | RCV001078158 | SCV001244209 | pathogenic | Congenital central hypoventilation | 2021-08-25 | no assertion criteria provided | literature only | |
| OMIM | RCV001078159 | SCV001244210 | pathogenic | Haddad syndrome | 2021-08-25 | no assertion criteria provided | literature only |