Submissions for variant NM_000383.4(AIRE):c.616G>A (p.Val206Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003063538	SCV003457797	uncertain significance	Polyglandular autoimmune syndrome, type 1	2022-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 206 of the AIRE protein (p.Val206Met). This variant is present in population databases (rs780838923, gnomAD 0.003%). 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.
CeGaT Center for Human Genetics Tuebingen	RCV003435863	SCV004153797	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing	AIRE: PM2, BP4