Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV000408586 | SCV000281894 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2016-01-01 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001074181 | SCV001239751 | pathogenic | Retinal dystrophy | 2019-02-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001380976 | SCV001579216 | pathogenic | not provided | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1507 of the ABCA4 protein (p.Gly1507Arg). This variant is present in population databases (rs568792949, gnomAD 0.1%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 23499370, 26593885, 27030965, 28041643). 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: 236115). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003401161 | SCV004122366 | likely pathogenic | Stargardt disease | 2023-10-30 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.4519G>A (p.Gly1507Arg) 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 allele was found at a frequency of 0.00016 in 172758 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ABCA4 causing Stargardt Disease (0.00016 vs 0.0014), allowing no conclusion about variant significance. c.4519G>A has been reported in the literature as a biallelic compound heterozygous genotype in individuals affected with Stargardt Disease (example, Fujinami_2013, Huckfeldt_2016, Lambertus_2016, Klufas_2018). 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: 28041643, 23499370, 27030965, 32307445, 28248825, 27699414, 26593885). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Dept Of Ophthalmology, |
RCV001074181 | SCV004707357 | uncertain significance | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
| NIHR Bioresource Rare Diseases, |
RCV000408586 | SCV000598976 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2015-01-01 | no assertion criteria provided | research |