Submissions for variant NM_000383.4(AIRE):c.1159G>A (p.Gly387Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003062998	SCV003450557	uncertain significance	Polyglandular autoimmune syndrome, type 1	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 387 of the AIRE protein (p.Gly387Ser). 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. 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 not expected to disrupt AIRE protein function. 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.
Ambry Genetics	RCV003062999	SCV003535370	uncertain significance	Inborn genetic diseases	2022-04-27	criteria provided, single submitter	clinical testing	The c.1159G>A (p.G387S) alteration is located in exon 10 (coding exon 10) of the AIRE gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the glycine (G) at amino acid position 387 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.