Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001976652 | SCV002264423 | uncertain significance | Aniridia 1; Irido-corneo-trabecular dysgenesis | 2021-08-05 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with arginine at codon 254 of the PAX6 protein (p.Ile254Arg). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and arginine. 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. 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 has not been reported in the literature in individuals with PAX6-related conditions. This variant is not present in population databases (ExAC no frequency). |