ClinVar Miner

Submissions for variant NM_003924.3(PHOX2B):c.753_767dup (p.Ala256_Ala260dup) (rs779557320)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000615033 SCV000712095 pathogenic Congenital central hypoventilation 2016-05-03 criteria provided, single submitter clinical testing The p.Ala241[25] variant in PHOX2B is a well-established pathogenic variant for CCHS, which has been reported in >100 affected individuals and was absent from ~ 4000 control chromosomes tested across multiple studies (Weese-Mayer 2010). This variant is a 15bp duplication within a polyalanine tract in exon 3 of the PHOX2 B gene, resulting in an expansion to a total of 25 alanine residues. It frequent ly occurs de novo, though autosomal dominant inheritance and somatic mosaicism h ave also been reported (Weese-Mayer 2010). While this variant typically causes c ongenital central hypoventilation, it has also been reported in individuals that presented with disease in infancy or childhood, raising the possibility of dela yed onset (Weese-Mayer 2010, Shimokaze 2015). In summary, this variant meets our criteria to be classified as pathogenic for CCHS in an autosomal dominant manne r.

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