Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostics Laboratory, |
RCV000761341 | SCV000891327 | likely pathogenic | Leber congenital amaurosis 13 | 2016-10-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000761341 | SCV001213448 | pathogenic | Leber congenital amaurosis 13 | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the RDH12 protein (p.Arg169Gln). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive Leber congenital amaurosis (PMID: 22065924, 25133751). ClinVar contains an entry for this variant (Variation ID: 623219). 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 with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg169 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been observed in individuals with RDH12-related conditions (PMID: 22065924, 26047050), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001073859 | SCV001239423 | pathogenic | Retinal dystrophy | 2018-07-13 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001530599 | SCV001745482 | likely pathogenic | not provided | 2021-06-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 22065924, 25133751, 24705292, 32172635, 27535533, 28559085, 30134391) |
Fulgent Genetics, |
RCV000761341 | SCV002794784 | pathogenic | Leber congenital amaurosis 13 | 2022-03-26 | criteria provided, single submitter | clinical testing | |
Al Jalila Children's Genomics Center, |
RCV001530599 | SCV002818221 | pathogenic | not provided | 2022-12-17 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000761341 | SCV004208586 | pathogenic | Leber congenital amaurosis 13 | 2023-08-29 | criteria provided, single submitter | clinical testing | |
Ocular Genomics Institute, |
RCV000761341 | SCV001146944 | likely pathogenic | Leber congenital amaurosis 13 | 2019-08-01 | no assertion criteria provided | clinical testing |