ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.344T>C (p.Ile115Thr)

gnomAD frequency: 0.00001  dbSNP: rs1645929674
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001377673 SCV001575064 pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2022-12-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RPE65 protein function. ClinVar contains an entry for this variant (Variation ID: 1066633). This missense change has been observed in individual(s) with inherited retinal dystrophy (PMID: 21211845, 26906952, 31174678). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 115 of the RPE65 protein (p.Ile115Thr).
Baylor Genetics RCV003469629 SCV004209250 pathogenic Leber congenital amaurosis 2 2023-12-13 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004596449 SCV005090709 likely pathogenic not provided 2024-07-31 criteria provided, single submitter clinical testing

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