ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1638A>T (p.Ter546Cys)

gnomAD frequency: 0.00001  dbSNP: rs386833673
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049633 SCV000220844 likely pathogenic Polyglandular autoimmune syndrome, type 1 2014-10-28 criteria provided, single submitter literature only
Labcorp Genetics (formerly Invitae), Labcorp RCV000049633 SCV004298123 likely pathogenic Polyglandular autoimmune syndrome, type 1 2023-09-04 criteria provided, single submitter clinical testing This variant results in an extension of the AIRE protein. Other variant(s) that result in a similarly extended protein product (p.*546Leuext*60) have been observed in individuals with AIRE-related disease (PMID: 28446514). This suggests that these extensions may be clinically significant. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 56222). This variant is also known as X546C. This protein extension has been observed in individuals with APECED (PMID: 9717837, 18728167). This variant is present in population databases (rs386833673, gnomAD 0.009%). This sequence change disrupts the translational stop signal of the AIRE mRNA. It is expected to extend the length of the AIRE protein by 60 additional amino acid residues.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049633 SCV000082040 probable-pathogenic Polyglandular autoimmune syndrome, type 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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