Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001235193 | SCV001407869 | pathogenic | not provided | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1118 of the ABCA4 protein (p.His1118Tyr). This variant is present in population databases (rs369440533, gnomAD 0.007%). This missense change has been observed in individuals with clinical features of Stargardt disease and inherited retinal dystrophy (PMID: 26551331, 30029497; Invitae). ClinVar contains an entry for this variant (Variation ID: 961495). 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.His1118 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25472526, 28559085). 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. |
| Gene |
RCV001235193 | SCV001764370 | likely pathogenic | not provided | 2021-05-11 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30029497, 33261146, 33090715, 26551331) |