Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
DBGen Ocular Genomics | RCV001591918 | SCV001816078 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2021-05-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001882714 | SCV002107536 | likely pathogenic | not provided | 2021-04-17 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Pro1088 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been observed in individuals with ABCA4-related conditions (PMID: 31543898, Invitae), which suggests that this may be a clinically significant amino acid residue. 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 has been observed in individual(s) with Stargardt disease (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 1088 of the ABCA4 protein (p.Pro1088Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. |