Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Molecular Genetics, |
RCV001352992 | SCV001548084 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2021-01-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002548492 | SCV003523328 | pathogenic | not provided | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2041 of the ABCA4 protein (p.Gly2041Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Stargardt disease (PMID: 18652558, 20801516, 31884623, 33546218). ClinVar contains an entry for this variant (Variation ID: 1048145). 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. This variant disrupts the p.Gly2041 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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. |