Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001075705 | SCV001241333 | pathogenic | Retinal dystrophy | 2019-04-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000085480 | SCV001380148 | pathogenic | not provided | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 821 of the ABCA4 protein (p.Trp821Arg). This variant is present in population databases (rs61749433, gnomAD 0.002%). This missense change has been observed in individual(s) with Stargardt disease or cone-rod dystrophy (PMID: 9973280, 22247458, 26593885; 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: 99136). 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. |
Gene |
RCV000085480 | SCV002504015 | pathogenic | not provided | 2021-11-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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: 11702214, 9973280, 11328725, 18652558, 24677105, 11527935, 25301883, 19265867, 11726554, 28430335, 29925512, 33375396, 26593885, 28365912, 25283059, 25474345, 29178665, 20128570, 22247458) |
Retina International | RCV000085480 | SCV000117617 | not provided | not provided | no assertion provided | not provided |