Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000085657 | SCV000229391 | pathogenic | not provided | 2015-02-24 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000177510 | SCV000281897 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2016-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000085657 | SCV001201993 | pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1532 of the ABCA4 protein (p.Asp1532Asn). This variant is present in population databases (rs62642574, gnomAD 0.2%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 9973280, 11726554, 19217903, 22589445, 24409374, 29925512; Invitae). 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: 99304). 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. |
Blueprint Genetics | RCV001074286 | SCV001239859 | pathogenic | Retinal dystrophy | 2019-05-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000085657 | SCV001769717 | pathogenic | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28118664, 9973280, 19217903, 22589445, 30055151, 29925512, 28559085, 29343940, 32013026, 31456290, 31589614, 32037395, 24409374, 33505770, 11726554) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235039 | SCV003934465 | pathogenic | Retinitis pigmentosa | 2023-05-30 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.4594G>A (p.Asp1532Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251478 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in ABCA4 causing Retinitis Pigmentosa (0.00011 vs 0.0014), allowing no conclusion about variant significance. c.4594G>A has been reported in the literature in multiple individuals affected with Stargardt disease and bull's eye maculopathy (examples: Lewis_1999, Shroyer_2001, Cella_2009, Giani_2012, Verdina_2014). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 11726554, 19217903 , 22589445, 24409374 , 9973280 ). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Institute of Human Genetics, |
RCV000177510 | SCV004032319 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2023-08-01 | criteria provided, single submitter | clinical testing | Criteria applied: PS4,PM2_SUP,PP3 |
Prevention |
RCV003421984 | SCV004118321 | pathogenic | ABCA4-related condition | 2023-07-10 | criteria provided, single submitter | clinical testing | The ABCA4 c.4594G>A variant is predicted to result in the amino acid substitution p.Asp1532Asn. This variant has previously been reported to be causative for autosomal recessive Stargardt disease (see for example - Gomes et al. 2009. PubMed ID: 19324865; Lewis et al. 1999. PubMed ID: 9973280; Schulz et al. 2017. PubMed ID: 28118664). This variant is reported in 0.21% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-94490550-C-T). This variant is interpreted as pathogenic. |
Retina International | RCV000085657 | SCV000117797 | not provided | not provided | no assertion provided | not provided | ||
Sharon lab, |
RCV001002826 | SCV001160843 | likely pathogenic | maculopathy | 2019-06-23 | no assertion criteria provided | research | |
Genome |
RCV001535669 | SCV001749732 | not provided | Cone-rod dystrophy 3; Retinitis pigmentosa 19; Age-related macular degeneration | no assertion provided | phenotyping only | Variant interpreted as Pathogenic and reported on 02-21-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |