Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV003460770 | SCV004190225 | pathogenic | RPE65-related recessive retinopathy | 2023-12-22 | reviewed by expert panel | curation | The RPE65 c.615_616del (p.Ile206fs) variant, previously known as 669delCA, is a frameshift variant that introduces a premature stop codon into exon 6 of 14, and is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PVS1). At least 1 patient with this variant exhibited nonrecordable ERG responses from rods (0.5 pts) and cones (1 pt), congenital night blindness (0.5 pts), onset between birth and five years (1 pt), decreased peripheral vision (1 pt), decreased central visual acuity (1 pt), and nystagmus (1 pt), which together are specific for RPE65-related recessive retinopathy (6 pts total, PMID: 11095629, PP4). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: PVS1, PM2_Supporting, PP4. (VCEP specifications version 1.0.0; date of approval 09/21/2023). |
| Invitae | RCV001388255 | SCV001589175 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2020-03-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RPE65 are known to be pathogenic (PMID: 9326941, 9501220, 9843205, 18632300). This variant has been observed in individual(s) with retinal dystrophy (PMID: 11095629). This variant is also known as 669delCA in the literature. ClinVar contains an entry for this variant (Variation ID: 98880). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile206Cysfs*27) in the RPE65 gene. It is expected to result in an absent or disrupted protein product. |
| Retina International | RCV000085210 | SCV000117347 | not provided | not provided | no assertion provided | not provided | ||
| Laboratory of Genetics in Ophthalmology, |
RCV001250700 | SCV001425575 | pathogenic | Leber congenital amaurosis 2 | no assertion criteria provided | research |