ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.254A>G (p.Tyr85Cys)

dbSNP: rs179363882
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000059056 SCV000227107 pathogenic not provided 2014-06-13 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000175592 SCV001194208 pathogenic Polyglandular autoimmune syndrome, type 1 2019-12-09 criteria provided, single submitter clinical testing NM_000383.3(AIRE):c.254A>G(Y85C) is classified as pathogenic in the context of autoimmune polyglandular syndrome type 1. Sources cited for classification include the following: PMID 12471056, 14974083, 16114041, 18708298 and 10677297. Classification of NM_000383.3(AIRE):c.254A>G(Y85C) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000175592 SCV001591355 pathogenic Polyglandular autoimmune syndrome, type 1 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 85 of the AIRE protein (p.Tyr85Cys). This variant is present in population databases (rs179363882, gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive AIRE-related conditions (PMID: 10677297, 12050215, 25367057). ClinVar contains an entry for this variant (Variation ID: 68222). 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: 12471056, 14974083, 16114041). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000175592 SCV002809937 likely pathogenic Polyglandular autoimmune syndrome, type 1 2022-01-13 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000059056 SCV004011367 pathogenic not provided 2023-07-01 criteria provided, single submitter clinical testing AIRE: PM3:Strong, PM1, PM2, PS3:Moderate
UniProtKB/Swiss-Prot RCV000059056 SCV000090577 not provided not provided no assertion provided not provided
Natera, Inc. RCV000175592 SCV002083848 pathogenic Polyglandular autoimmune syndrome, type 1 2020-06-10 no assertion criteria provided clinical testing

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