Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000970746 | SCV001118342 | likely benign | Polyglandular autoimmune syndrome, type 1 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001420757 | SCV001623103 | uncertain significance | not specified | 2021-04-26 | criteria provided, single submitter | clinical testing | Variant summary: AIRE c.1118C>T (p.Ala373Val) results in a non-conservative amino acid change located in the PRR domain (Suspitsin_2020) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00061 in 279934 control chromosomes in the gnomAD database, including one homozygote. This frequency is not higher than expected for a pathogenic variant in AIRE causing Autoimmune Polyglandular Syndrome Type 1 (0.00061 vs 0.0028), allowing no conclusion about variant significance. c.1118C>T has been reported in the literature in one individual affected with chronic mucocutaneous candidiasis (Suspitsin_2020). The report does not provide unequivocal conclusions about association of the variant with Autoimmune Polyglandular Syndrome Type 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV000970746 | SCV001464220 | likely benign | Polyglandular autoimmune syndrome, type 1 | 2020-04-29 | no assertion criteria provided | clinical testing |