Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000085804 | SCV000344272 | uncertain significance | not provided | 2016-09-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000085804 | SCV000616627 | pathogenic | not provided | 2017-10-24 | criteria provided, single submitter | clinical testing | The E2096K variant in the ABCA4 gene has been published previously in association with Stargardt disease (Lewis et al., 1999; Shroyer et al., 2001; Utz et al., 2013). The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). E2096K 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. Additionally, E2096K has been shown to significantly reduce ATPase activity of the ABCA4 protein (Sun et al., 2000). In summary, we consider this variant to be pathogenic |
| Knight Diagnostic Laboratories, |
RCV000085804 | SCV001448852 | pathogenic | not provided | 2019-06-19 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000085804 | SCV004292358 | pathogenic | not provided | 2023-06-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ABCA4 function (PMID: 11017087). 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. ClinVar contains an entry for this variant (Variation ID: 99445). This missense change has been observed in individual(s) with Stargardt disease (PMID: 11726554, 29925512, 33691693). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs61750646, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2096 of the ABCA4 protein (p.Glu2096Lys). |
| Retina International | RCV000085804 | SCV000117947 | not provided | not provided | no assertion provided | not provided |