Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV000408519 | SCV000281907 | likely pathogenic | Stargardt disease 1 | 2016-01-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000085683 | SCV000321353 | pathogenic | not provided | 2018-10-04 | criteria provided, single submitter | clinical testing | The R1640W pathogenic variant in the ABCA4 gene has been reported previously in autosomal recessive Stargardt disease in affected individuals when in the homozgyous state or when in trans with another pathogenic variant (Battu et al., 2015; Fujinami et al., 2013; Rozet et al., 1998). The R1640W variant has been reported on the same allele (in cis) with the W1408R variant in families with Stargardt disease, and in a family presenting with both Stargardt disease and retinitis pigmentosa, when in trans with another pathogenic variant (Valverde et al, 2006; Shroyer et al, 2001). Shroyer et al. (2001) showed very little protein from cells transfected with the W1408R and R1640W variants in cis; however, proteins bearing only the W1408R or the R1640W variants appear to have mild or moderate defects in expression or stability. The R1640W variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1640W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. We interpret R1640W as a pathogenic variant. |
EGL Genetic Diagnostics, |
RCV000085683 | SCV000339315 | other | not provided | 2017-08-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000085683 | SCV001210838 | pathogenic | not provided | 2019-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 1640 of the ABCA4 protein (p.Arg1640Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs61751404, ExAC 0.001%). This variant has been observed in many individuals affected with ABCA4-related conditions. While this variant is commonly found in cis with the variant p.Trp1408Arg, it has also been observed without p.Trp1408Arg in affected individuals (PMID: 28041643, 28559085, 29925512, 9781034). ClinVar contains an entry for this variant (Variation ID: 99330). This variant has been reported to affect ABCA4 protein function (PMID: 11687513). This variant disrupts the p.Arg1640 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11527935, 26103963, 23755871, 10711710, 28118664). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV000210311 | SCV001239246 | pathogenic | Retinal dystrophy | 2019-08-16 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000085683 | SCV001447306 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Retina International | RCV000085683 | SCV000117823 | not provided | not provided | no assertion provided | not provided | ||
Centre for Genomic Medicine, |
RCV000210311 | SCV000259103 | pathogenic | Retinal dystrophy | 2015-01-30 | no assertion criteria provided | clinical testing | |
NIHR Bioresource Rare Diseases, |
RCV000505114 | SCV000598986 | likely pathogenic | Leber congenital amaurosis | 2015-01-01 | no assertion criteria provided | research | |
Medical Genetics Laboratory, |
RCV000787504 | SCV000926470 | pathogenic | Stargardt disease | 2018-04-01 | no assertion criteria provided | research | |
Sharon lab, |
RCV000787504 | SCV001160839 | pathogenic | Stargardt disease | 2019-06-23 | no assertion criteria provided | research |