Submissions for variant NM_000383.4(AIRE):c.1163_1164insA (p.Met388fs)

gnomAD frequency: 0.00001  dbSNP: rs386833672

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000049632	SCV000486854	pathogenic	Polyglandular autoimmune syndrome, type 1	2016-08-23	criteria provided, single submitter	clinical testing
Invitae	RCV000049632	SCV001406890	pathogenic	Polyglandular autoimmune syndrome, type 1	2023-09-15	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 56221). This sequence change creates a premature translational stop signal (p.Met388Ilefs*36) in the AIRE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AIRE are known to be pathogenic (PMID: 11524731, 26141571). This variant is present in population databases (rs386833672, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with autoimmune polyendocrinopathy syndrome (PMID: 9398840, 18708298, 28919897). This variant is also known as an A insertion at the position 1284. For these reasons, this variant has been classified as Pathogenic.
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health	RCV000049632	SCV004036174	pathogenic	Polyglandular autoimmune syndrome, type 1	2023-09-14	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049632	SCV000082039	probable-pathogenic	Polyglandular autoimmune syndrome, type 1		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.