Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003788943 | SCV004572440 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2023-07-17 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt RPE65 protein function. This variant has not been reported in the literature in individuals affected with RPE65-related conditions. This variant is present in population databases (rs143435745, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 453 of the RPE65 protein (p.Lys453Glu). |