ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.499G>T (p.Asp167Tyr) (rs61752883)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085203 SCV000491115 likely pathogenic not provided 2016-08-03 criteria provided, single submitter clinical testing The D167Y variant in the RPE65 gene has been reported previously in the heterozygous state along with a second RPE65 variant in a few unrelated individuals with retinal dystrophy and Leber congenital amaurosis; however, the phase of the variants was not confirmed in all cases (Thompson et al., 2000; Simonelli et al., 2007; Henderson et al., 2007; Ripamonti et al., 2014). The D167Y variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D167Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D167Y as a likely pathogenic variant.
Human Genetics - Radboudumc,Radboudumc RCV000678617 SCV000804705 uncertain significance Retinitis pigmentosa 20 2016-09-01 no assertion criteria provided clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778252 SCV000914424 likely pathogenic RPE65-Related Disorders 2018-12-11 criteria provided, single submitter clinical testing The RPE65 c.499G>T (p.Asp167Tyr) variant is a missense variant that has been reported in a compound heterozygous state in three individuals with either Leber congenital amaurosis or retinal dystrophy (Thompson et al. 2000; Simonelli et al. 2007; Bainbridge et al. 2008; Ripamonti et al. 2014). The p.Asp167Tyr variant was also identified in a heterozygous state in one additional case in whom a second variant was not identified (Henderson et al. 2007). The p.Asp167Tyr variant was absent from 50 control individuals but was reported at a frequency of 0.000026 in the European (non-Finnish) population of the Genome Aggregation Database. Functional studies of this variant have not been conducted, but it affects a conserved residue and in silico tools predict it to have a damaging effect. Based on the collective evidence, the p.Asp167Tyr variant is classified as likely pathogenic for RPE65-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Retina International RCV000085203 SCV000117340 not provided not provided no assertion provided not provided

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