ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.268T>C (p.Tyr90His) (rs1555871902)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000515130 SCV000609490 likely pathogenic Polyglandular autoimmune syndrome, type 1 2017-10-31 criteria provided, single submitter clinical testing The c.268T>C; p.Tyr90His is a missense variant in the AIRE gene. It lies within the caspase activation and recruitment domain (CARD) which is required for the localization and export of AIRE protein from cytoplasm to the nucleus as well as homodimerization (Passos et al 2017). The majority of the reported disease causing variants in the HSR domain are missense changes, thus supporting that this region is missense intolerant. A variant at the same location with a different amino acid change, p.Tyr90Cys, has been previously reported as pathogenic (Pearce et al 1998; Peterson et al 2004). This variant was observed in trans with a pathogenic AIRE variant. The c.268T>C variant is absent from population databases suggesting it is a rare variant. In silico analyses are predicted to be damaging. Based on the combined evidence, this variant is classified as likely pathogenic

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