Submissions for variant NM_000383.4(AIRE):c.102C>A (p.Asp34Glu)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002802076	SCV003199953	uncertain significance	Polyglandular autoimmune syndrome, type 1	2022-07-27	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 34 of the AIRE protein (p.Asp34Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal recessive autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia (Invitae). 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. This variant disrupts the p.Asp34 amino acid residue in AIRE. Other variant(s) that disrupt this residue have been observed in individuals with AIRE-related conditions (PMID: 24703644; Invitae), which suggests that this may be a clinically significant amino acid residue. 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.