Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001075351 | SCV001240972 | likely pathogenic | Retinal dystrophy | 2018-05-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001212314 | SCV001383894 | pathogenic | Leber congenital amaurosis 13 | 2023-08-14 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with autosomal recessive inherited retinal dystrophy including Leber congenital amaurosis (PMID: 22065924, 23661369, 30134391). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 169 of the RDH12 protein (p.Arg169Trp). This variant is present in population databases (no rsID available, gnomAD 0.004%). ClinVar contains an entry for this variant (Variation ID: 866945). 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.Arg169 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22065924, 25133751). 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. |
Ophthalmic Genetics Group, |
RCV003324554 | SCV004030286 | pathogenic | Leber congenital amaurosis | 2023-07-24 | criteria provided, single submitter | research | Clinical significance based on ACMG v2.0 |
Baylor Genetics | RCV001212314 | SCV004208589 | pathogenic | Leber congenital amaurosis 13 | 2023-08-15 | criteria provided, single submitter | clinical testing |