Submissions for variant NM_000383.4(AIRE):c.560C>T (p.Ser187Leu)

gnomAD frequency: 0.00012  dbSNP: rs143952576

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000800560	SCV000940284	uncertain significance	Polyglandular autoimmune syndrome, type 1	2022-10-27	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 187 of the AIRE protein (p.Ser187Leu). This variant is present in population databases (rs143952576, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. ClinVar contains an entry for this variant (Variation ID: 646302). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc.	RCV000800560	SCV002083860	uncertain significance	Polyglandular autoimmune syndrome, type 1	2020-02-26	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965594	SCV004792378	likely benign	AIRE-related disorder	2023-12-22	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).