Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV000408446 | SCV000281946 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2016-01-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000480932 | SCV000564540 | likely pathogenic | not provided | 2014-01-04 | criteria provided, single submitter | clinical testing | The L2026P missense variant has not been reported previously as a pathogenic variant or as a benign polymorphism to our knowledge. The L2026P amino acid substitution is semi-conservative since there is no change in charge or polarity, although the unique structure of the Proline residue may affect the secondary structure of the protein. The position at which this substitution occurs is conserved in the protein and other missense variants in nearby codons (L2027F, R2030Q) have been reported in association with Stargardt disease (Lewis et al., 1999; Webster et al., 2001; Briggs et al., 2001). Additionally, the L2026P variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. Therefore, the L2026P missense change is a strong candidate for a pathogenic variant, although the possibility that it is a benign polymorphism can not be excluded. |
| Fulgent Genetics, |
RCV000763439 | SCV000894206 | likely pathogenic | Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000480932 | SCV002263505 | pathogenic | not provided | 2024-02-07 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2026 of the ABCA4 protein (p.Leu2026Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 29854428, 29925512, 34214897). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 236144). 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%. For these reasons, this variant has been classified as Pathogenic. |
| Institute of Human Genetics, |
RCV004816431 | SCV005068534 | likely pathogenic | Retinal dystrophy | 2021-01-01 | criteria provided, single submitter | clinical testing |