ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.47C>T (p.Thr16Met)

dbSNP: rs179363877
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001037856 SCV001201288 pathogenic Polyglandular autoimmune syndrome, type 1 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 16 of the AIRE protein (p.Thr16Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia (PMID: 11524733, 21932610, 25361846, 28911151). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68227). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AIRE protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects AIRE function (PMID: 14974083). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001037856 SCV002024151 pathogenic Polyglandular autoimmune syndrome, type 1 2020-12-14 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001037856 SCV002804859 pathogenic Polyglandular autoimmune syndrome, type 1 2021-08-11 criteria provided, single submitter clinical testing
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health RCV001037856 SCV004036186 pathogenic Polyglandular autoimmune syndrome, type 1 2023-09-14 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059061 SCV000090582 not provided not provided no assertion provided not provided
Natera, Inc. RCV001037856 SCV002083839 pathogenic Polyglandular autoimmune syndrome, type 1 2021-03-21 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004754293 SCV005364453 pathogenic AIRE-related disorder 2024-04-17 no assertion criteria provided clinical testing The AIRE c.47C>T variant is predicted to result in the amino acid substitution p.Thr16Met. This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with autoimmune polyendocrinopathy syndrome (Table 1, Cihakova et al. 2001. PubMed ID: 11524733; Table 2, Podkrajsek et al. 2005. PubMed ID: 15886230; Table 1, Kollios et al. 2011. PubMed ID: 21932610). This variant has not been reported in a large population database, indicating this variant is rare. An in vitro experimental study suggests this variant disrupts the homomultimerization of the protein (Figure 5, Halonen et al. 2004. PubMed ID: 14974083). This variant is interpreted as pathogenic.

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