Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001756442 | SCV001985203 | uncertain significance | not provided | 2020-06-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Labcorp Genetics |
RCV001756442 | SCV002171013 | pathogenic | not provided | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2037 of the ABCA4 protein (p.Ala2037Thr). This variant is present in population databases (rs756555985, gnomAD 0.01%). This missense change has been observed in individual(s) with Stargardt disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 1302943). 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.Ala2037 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30060493). 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. |