ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.510_522dup (p.Leu175fs)

dbSNP: rs940485051
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482743 SCV000573858 pathogenic not provided 2018-06-05 criteria provided, single submitter clinical testing The c.510_522dup13 variant in the AIRE gene has been reported previously, as c.522_523ins13 using alternate nomenclature, in a patient with APECED who also harbored a second pathogenic variant in the AIRE gene with unknown phase (Ferre et al., 2016). The c.510_522dup13 variant causes a frameshift starting with codon Leucine 175, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 46 of the new reading frame, denoted p.Leu175ArgfsX46. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.510_522dup13 variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.510_522dup13 as a pathogenic variant.
Invitae RCV001201790 SCV001372881 pathogenic Polyglandular autoimmune syndrome, type 1 2023-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu175Argfs*46) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (PMID: 27588307). This variant is also known as c.522_523ins13. ClinVar contains an entry for this variant (Variation ID: 424080). For these reasons, this variant has been classified as Pathogenic.
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health RCV001201790 SCV004036200 pathogenic Polyglandular autoimmune syndrome, type 1 2023-09-14 criteria provided, single submitter clinical testing

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