ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.1543C>T (p.Arg515Trp) (rs121917745)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000816506 SCV000957019 likely pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 515 of the RPE65 protein (p.Arg515Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121917745, ExAC 0.003%). This variant has been observed in the homozygous state or in combination with another RPE65 variant in individuals affected with Leber congenital amaurosis or retinitis pigmentosa (PMID: 15557452, 25495949, 26626312, 26906952, 29681726). ClinVar contains an entry for this variant (Variation ID: 13120). This variant has been reported to impair RPE65 protein localization and to increase protein degradation (PMID: 25752820). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000013999 SCV000034246 pathogenic Retinitis pigmentosa 20 2004-12-01 no assertion criteria provided literature only
OMIM RCV000014000 SCV000034247 pathogenic Leber congenital amaurosis 2 2004-12-01 no assertion criteria provided literature only
Retina International RCV000085176 SCV000117313 not provided not provided no assertion provided not provided
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132583 SCV000172526 pathogenic Retinitis pigmentosa no assertion criteria provided not provided Converted during submission to Pathogenic.

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