ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.746A>G (p.Tyr249Cys)

dbSNP: rs373652862
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001206748 SCV001378070 pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2023-10-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 249 of the RPE65 protein (p.Tyr249Cys). This variant is present in population databases (rs373652862, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individuals with Leber congenital amaurosis (PMID: 26906952, 28130426). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 937681). 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. Experimental studies have shown that this missense change affects RPE65 function (PMID: 25752820). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003469337 SCV004209244 pathogenic Leber congenital amaurosis 2 2023-08-14 criteria provided, single submitter clinical testing
Natera, Inc. RCV001833815 SCV002092759 pathogenic Leber congenital amaurosis 2021-05-21 no assertion criteria provided 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.