Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000542988 | SCV000629959 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 309 of the AIRE protein (p.Ile309Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with AIRE-related disease (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 458620). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Athena Diagnostics | RCV000710498 | SCV000840733 | uncertain significance | not provided | 2018-05-23 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003278883 | SCV003987427 | uncertain significance | Inborn genetic diseases | 2023-06-12 | criteria provided, single submitter | clinical testing | The c.925A>G (p.I309V) alteration is located in exon 8 (coding exon 8) of the AIRE gene. This alteration results from a A to G substitution at nucleotide position 925, causing the isoleucine (I) at amino acid position 309 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000542988 | SCV002083881 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2020-02-02 | no assertion criteria provided | clinical testing |