Submissions for variant NM_000383.4(AIRE):c.278T>G (p.Leu93Arg)

dbSNP: rs179363884

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002514297	SCV003444330	pathogenic	Polyglandular autoimmune syndrome, type 1	2023-09-29	criteria provided, single submitter	clinical testing	This variant is also known as c.398T>G. For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 68224). This missense change has been observed in individual(s) with autoimmune polyendocrinopathy syndrome (PMID: 10084559). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 93 of the AIRE protein (p.Leu93Arg).
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health	RCV002514297	SCV004036194	likely pathogenic	Polyglandular autoimmune syndrome, type 1	2023-09-14	criteria provided, single submitter	clinical testing
UniProtKB/Swiss-Prot	RCV000059058	SCV000090579	not provided	not provided		no assertion provided	not provided