ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.617T>C (p.Ile206Thr)

gnomAD frequency: 0.00004  dbSNP: rs768445391
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001073324 SCV001238863 likely pathogenic Retinal dystrophy 2018-11-20 criteria provided, single submitter clinical testing
Invitae RCV001208105 SCV001379477 likely pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 206 of the RPE65 protein (p.Ile206Thr). This variant is present in population databases (rs768445391, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of autosomal recessive inherited retinal dystrophy (PMID: 32037395; Invitae). ClinVar contains an entry for this variant (Variation ID: 829832). 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 not expected to disrupt RPE65 protein function with a negative predictive value of 80%. 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.
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV001029769 SCV001192547 likely pathogenic Retinitis pigmentosa 20 2019-04-09 no assertion criteria provided clinical testing
Natera, Inc. RCV001836068 SCV002092765 uncertain significance Leber congenital amaurosis 2020-07-23 no assertion criteria provided clinical testing

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