Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003764654 | SCV004570787 | pathogenic | Aniridia 1; Irido-corneo-trabecular dysgenesis | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 38 of the PAX6 protein (p.Arg38Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of aniridia (PMID: 17406642, 19876904, 31700164). ClinVar contains an entry for this variant (Variation ID: 40090). 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. This variant disrupts the p.Arg38 amino acid residue in PAX6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29145603, 29914532, 31700164, 34415986; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000033168 | SCV000056950 | pathogenic | Aniridia 1 | 2009-11-01 | no assertion criteria provided | literature only | |
OMIM | RCV003883464 | SCV004697962 | pathogenic | Coloboma, ocular, autosomal dominant | 2009-11-01 | no assertion criteria provided | literature only |