ClinVar Miner

Submissions for variant NM_152443.3(RDH12):c.226G>T (p.Gly76Trp)

dbSNP: rs368489658
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001377219 SCV001574493 pathogenic Leber congenital amaurosis 13 2023-07-10 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 76 of the RDH12 protein (p.Gly76Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive inherited retinal dystrophy (PMID: 30718709; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 636078). 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 expected to disrupt RDH12 protein function. This variant disrupts the p.Gly76 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19956407, 24265693, 30134391). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001377219 SCV004208564 likely pathogenic Leber congenital amaurosis 13 2023-10-12 criteria provided, single submitter clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787671 SCV000926661 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Natera, Inc. RCV001830679 SCV002091259 likely pathogenic Leber congenital amaurosis 2020-03-29 no assertion criteria provided clinical testing

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