ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.1102T>C (p.Tyr368His) (rs62653011)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genetics - Radboudumc,Radboudumc RCV000022749 SCV000804702 pathogenic Retinitis pigmentosa 20 2016-09-01 no assertion criteria provided clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000348257 SCV000358873 pathogenic RPE65-Related Disorders 2017-04-27 criteria provided, single submitter clinical testing Across a selection of available literature, the RPE65 c.1102T>C (p.Tyr368His) missense variant has been identified in a total of 25 individuals with RPE65-related disorders including in 17 individuals in a homozygous state, in 8 individuals in a compound heterozygous state. Phenotypes of the affected individuals included congenital retinal dystrophy and Leber congenital amaurosis. The variant was also detected in a heterozygous state in five unaffected family members (Felius et al. 2002; Yzer et al. 2003; Sundaresan et al. 2009; Ripamonti et al. 2014; Astuti et al. 2016). The p.Tyr368His variant was found in a heterozygous state in three of 2291 controls and is reported at a frequency of 0.00012 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional studies in cell lines demonstrated that the p.Tyr368His variant significantly reduced enzymatic activity compared to wild type RPE65 and had decreased protein stability (Takahashi et al. 2006; Li et al. 2014). In vivo functional studies also showed that the p.Tyr368His variant reduced enzymatic activity after subretinal injection into Rpe65 knockout mice (Takahashi et al. 2006). Based on the collective evidence, the p.Tyr368His variant is classified as pathogenic for RPE65-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787920 SCV000926939 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
OMIM RCV000022749 SCV000044038 pathogenic Retinitis pigmentosa 20 2003-09-01 no assertion criteria provided literature only
OMIM RCV000022750 SCV000044039 pathogenic Leber congenital amaurosis 2 2003-09-01 no assertion criteria provided literature only
Retina International RCV000085150 SCV000117287 not provided not provided no assertion provided not provided

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