Submissions for variant NM_000383.4(AIRE):c.1480_1483del (p.Arg494fs)

dbSNP: rs1057517072

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000409587	SCV000486702	likely pathogenic	Polyglandular autoimmune syndrome, type 1	2016-07-20	criteria provided, single submitter	clinical testing
Invitae	RCV000409587	SCV002183465	pathogenic	Polyglandular autoimmune syndrome, type 1	2021-06-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg494Trpfs*26) in the AIRE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the AIRE protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the AIRE protein. Other variant(s) that disrupt this region (p.Pro539Leu) have been determined to be pathogenic (PMID: 11836330, 28446514, 17289071, 21295522, 15811934). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with AIRE-related conditions. ClinVar contains an entry for this variant (Variation ID: 371185).
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health	RCV000409587	SCV004036178	pathogenic	Polyglandular autoimmune syndrome, type 1	2023-09-14	criteria provided, single submitter	clinical testing