Submissions for variant NM_000383.4(AIRE):c.1384G>A (p.Gly462Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003066566	SCV003444255	uncertain significance	Polyglandular autoimmune syndrome, type 1	2024-10-28	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 462 of the AIRE protein (p.Gly462Ser). This variant is present in population databases (rs540790785, gnomAD 0.005%). 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: 2139326). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt AIRE protein function with a negative predictive value of 95%. 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.
PreventionGenetics, part of Exact Sciences	RCV003410053	SCV004106281	uncertain significance	AIRE-related disorder	2022-10-05	criteria provided, single submitter	clinical testing	The AIRE c.1384G>A variant is predicted to result in the amino acid substitution p.Gly462Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0051% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-45713777-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.