Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000430954 | SCV000532302 | likely pathogenic | not provided | 2017-03-21 | criteria provided, single submitter | clinical testing | The D846V variant in the ABCA4 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D846V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). D846V 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, this variant is likely pathogenic. |
Blueprint Genetics | RCV001074641 | SCV001240233 | likely pathogenic | Retinal dystrophy | 2019-02-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000430954 | SCV002299865 | pathogenic | not provided | 2023-08-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 846 of the ABCA4 protein (p.Asp846Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Stargardt disease (PMID: 27939946, 30718709, 33851411). ClinVar contains an entry for this variant (Variation ID: 389679). 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. |
Department of Clinical Genetics, |
RCV000787485 | SCV000926451 | likely pathogenic | Retinitis pigmentosa | 2018-04-01 | no assertion criteria provided | research |