ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.44G>T (p.Arg15Leu)

dbSNP: rs179363876
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001378939 SCV001576640 pathogenic Polyglandular autoimmune syndrome, type 1 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 15 of the AIRE protein (p.Arg15Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive autoimmune polyendocrinopathy type 1 (PMID: 9837820). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 68226). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AIRE protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects AIRE function (PMID: 14974083, 15712268). For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059060 SCV000090581 not provided not provided no assertion provided not provided
Natera, Inc. RCV001378939 SCV002083838 likely pathogenic Polyglandular autoimmune syndrome, type 1 2020-04-14 no assertion criteria provided clinical testing

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