Description
This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 162 of the RPE65 protein (p.Thr162Pro). This variant is present in population databases (rs774309607, gnomAD 0.002%). This missense change has been observed in individual(s) with Leber congenital amaurosis or retinitis pigmentosa (PMID: 17964524, 20079931; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 870346). 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 with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
# | Sample | Method | Observation |
---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
---|
1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |