Submissions for variant NM_000383.4(AIRE):c.1115C>T (p.Ser372Leu)

gnomAD frequency: 0.00010  dbSNP: rs202237214

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001244172	SCV001417374	uncertain significance	Polyglandular autoimmune syndrome, type 1	2022-10-28	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 372 of the AIRE protein (p.Ser372Leu). This variant is present in population databases (rs202237214, gnomAD 0.02%). 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: 968931). 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.
Fulgent Genetics, Fulgent Genetics	RCV001244172	SCV002779795	uncertain significance	Polyglandular autoimmune syndrome, type 1	2021-09-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002568576	SCV003704991	uncertain significance	Inborn genetic diseases	2022-09-26	criteria provided, single submitter	clinical testing	The c.1115C>T (p.S372L) alteration is located in exon 10 (coding exon 10) of the AIRE gene. This alteration results from a C to T substitution at nucleotide position 1115, causing the serine (S) at amino acid position 372 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001700992	SCV001926964	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001700992	SCV001966361	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001244172	SCV002083896	uncertain significance	Polyglandular autoimmune syndrome, type 1	2020-01-17	no assertion criteria provided	clinical testing