Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001851621 | SCV002243662 | pathogenic | Aniridia 1; Irido-corneo-trabecular dysgenesis | 2022-09-28 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with foveal hypoplasia (PMID: 8640214, 32360764). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg128 amino acid residue in PAX6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18332330). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects PAX6 function (PMID: 14744876, 23404109, 27013732). 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 PAX6 protein function. ClinVar contains an entry for this variant (Variation ID: 3470). This variant is also known as R125C. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 128 of the PAX6 protein (p.Arg128Cys). |
| OMIM | RCV000003635 | SCV000023798 | pathogenic | Foveal hypoplasia 1 | 1996-06-01 | no assertion criteria provided | literature only | |
| Wessex Regional Genetics Laboratory, |
RCV000984410 | SCV001055763 | pathogenic | Aniridia 1 | 2019-08-15 | no assertion criteria provided | clinical testing |