Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV000408546 | SCV000281839 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2016-01-01 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000085452 | SCV000574771 | pathogenic | not provided | 2023-04-01 | criteria provided, single submitter | clinical testing | ABCA4: PM3:Very Strong, PM2, PM5, PP4, PS3:Supporting |
Fulgent Genetics, |
RCV000763047 | SCV000893528 | likely pathogenic | Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000085452 | SCV001202188 | pathogenic | not provided | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 653 of the ABCA4 protein (p.Arg653Cys). This variant is present in population databases (rs61749420, gnomAD 0.003%). This missense change has been observed in individual(s) with cone rod dystrophy and Stargardt disease (PMID: 23776498, 28559085). 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: 99108). 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 ABCA4 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg653 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9466990, 10413692, 19074458). 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. |
Blueprint Genetics | RCV001074668 | SCV001240260 | pathogenic | Retinal dystrophy | 2019-03-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000085452 | SCV001446861 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Institute of Medical Molecular Genetics, |
RCV000408546 | SCV001548139 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2021-01-30 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000085452 | SCV001782833 | pathogenic | not provided | 2021-08-11 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33375396, 10958763, 33301772, 28559085, 23776498, 29925512, 32619608, 30204727, 23982839, 18652558, 25444351, 25097154, 23953153, 19265867, 15192030, 28355279, 27939946, 23499370, 11702214, 26957898, 26992781) |
Retina International | RCV000085452 | SCV000117589 | not provided | not provided | no assertion provided | not provided | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000085452 | SCV001957874 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000085452 | SCV001968217 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |