ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.1292A>G (p.Tyr431Cys) (rs62636300)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001054426 SCV001218739 pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 431 of the RPE65 protein (p.Tyr431Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs62636300, ExAC 0.002%). This variant has been observed in individual(s) with Leber congenital amaurosis or clinical features of inherited retinal dystrophy (PMID: 14962443, 19117922, 30268864, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 29873). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000022754 SCV000044043 pathogenic Leber congenital amaurosis 2 2004-02-01 no assertion criteria provided literature only
Retina International RCV000085161 SCV000117298 not provided not provided no assertion provided not provided

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