Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Molecular Genetics, |
RCV001353029 | SCV001548142 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2021-01-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001871909 | SCV002233070 | pathogenic | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | 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. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1048167). This missense change has been observed in individual(s) with Stargardt Disease (PMID: 28559085). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 978 of the ABCA4 protein (p.Gly978Ser). |