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

dbSNP: rs179363882

Total submissions: 7

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.
Labcorp Genetics (formerly Invitae), Labcorp	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