Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000085788 | SCV003523317 | likely pathogenic | not provided | 2023-10-26 | 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 2035 of the ABCA4 protein (p.Leu2035Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of ABCA4-related conditions and/or Stargardt disease (PMID: 11527935, 14517951, 36909829). ClinVar contains an entry for this variant (Variation ID: 99429). 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%. 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. |
| Ophthalmic Genetics Group, |
RCV003324514 | SCV004030356 | likely pathogenic | Stargardt disease | 2023-07-24 | criteria provided, single submitter | research | Clinical significance based on ACMG v2.0 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003324514 | SCV005726782 | likely pathogenic | Stargardt disease | 2024-11-11 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.6104T>C (p.Leu2035Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251380 control chromosomes (gnomAD). c.6104T>C has been reported in the literature in individuals affected with Stargardt Disease (Briggs_2001, Jaakson_2003, Mena_2021, Peter_2023). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 11527935, 14517951, 33841504, 36909829). ClinVar contains an entry for this variant (Variation ID: 99429). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Retina International | RCV000085788 | SCV000117930 | not provided | not provided | no assertion provided | not provided |