ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.825C>A (p.Tyr275Ter)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen RCV003881705 SCV004697431 pathogenic RPE65-related recessive retinopathy 2024-02-20 reviewed by expert panel curation The NM_000329.3(RPE65):c.825C>A (p.Tyr275Ter) variant is a nonsense variant that introduces a premature stop codon into exon 8 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). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). At least one proband harboring this variant exhibits a phenotype including congenital night blindness (0.5 pts), extinguished rod ERG responses (0.5 pts), previous exome sequencing that did not provide an alternative explanation for visual impairment (2 pts), symptomatic onset between birth and age five years (1 pt), retinal degeneration with attenuated vessels (0.5 pts), and extinguished cone ERG responses (1 pt), which together are specific for RPE65-related recessive retinopathy (5.5 points, PMID: 31273949, PP4). 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).
Baylor Genetics RCV004573380 SCV005055448 pathogenic Leber congenital amaurosis 2 2023-11-17 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.