ClinVar Miner

Submissions for variant NM_003924.4(PHOX2B):c.776_777insGGCGGCCGCGGCAGCGGCGGC (p.Ala260_Gly261insAlaAlaAlaAlaAlaAlaAla)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002409719 SCV002672194 pathogenic Hereditary cancer-predisposing syndrome 2017-10-25 criteria provided, single submitter clinical testing The p.Ala241[27] pathogenic mutation, located in coding exon 3 of the PHOX2B gene, results from an expansion of the polyalanine repeat region from 20 to 27 repeats. This expansion mutation is associated with congenital central hypoventilation syndrome (Amiel J et al. Nat. Genet., 2003 Apr;33:459-61; Matera I et al. J. Med. Genet., 2004 May;41:373-80). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
PreventionGenetics, part of Exact Sciences RCV004753556 SCV005360239 pathogenic PHOX2B-related disorder 2024-06-14 no assertion criteria provided clinical testing The PHOX2B c.776_777insGGCGGCCGCGGCAGCGGCGGC variant is predicted to result in an in-frame amino acid insertion (p.Ala254_Ala260dup). This variant results in an expansion of the polyalanine repeat region from 20 repeats (normal) to 27 repeats (abnormal). An expansion of this size has previously been reported to be causative for CCHS and has also been associated with Hirschsprung Disease (Lai and Schroer. 2008. PubMed ID: 18230845, Serra et al. 2010. PubMed ID: 20456320). This variant has not been reported in a large population database, indicating it is rare. This variant is interpreted as pathogenic.

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