Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001388257 | SCV001589177 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2023-03-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RPE65 function (PMID: 16150724). 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 RPE65 protein function. ClinVar contains an entry for this variant (Variation ID: 98875). This missense change has been observed in individual(s) with autosomal recessive retinitis pigementosa or Leber congenital amaurosis (PMID: 9501220, 27874104). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs61752884, gnomAD 0.01%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 182 of the RPE65 protein (p.His182Tyr). |
| Retina International | RCV000085205 | SCV000117342 | not provided | not provided | no assertion provided | not provided | ||
| Faculty of Health Sciences, |
RCV001257821 | SCV001434605 | pathogenic | Autosomal recessive retinitis pigmentosa | 2016-11-22 | no assertion criteria provided | literature only |