Submissions for variant NM_000383.4(AIRE):c.440C>T (p.Thr147Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002643964	SCV003512153	uncertain significance	Polyglandular autoimmune syndrome, type 1	2022-04-04	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 147 of the AIRE protein (p.Thr147Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. 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 tolerated. 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.
Illumina Laboratory Services, Illumina	RCV003126273	SCV003802838	uncertain significance	not provided	2022-10-10	criteria provided, single submitter	clinical testing	The AIRE c.440C>T (p.Thr147Ile) missense variant results in the substitution of threonine at amino acid position 147 with isoleucine. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.440C>T (p.Thr147Ile) variant is classified as a variant of uncertain significance for autoimmune polyendocrinopathy syndrome.