Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000085559 | SCV000577305 | pathogenic | not provided | 2023-07-11 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 15192030, 23341817, 26720470, 31589614, 35156991, 33301772, 9973280, 29555955) |
Invitae | RCV000085559 | SCV001580409 | pathogenic | not provided | 2023-05-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 99208). This missense change has been observed in individual(s) with ABCA4-related inherited retinal dystrophies (PMID: 9973280, 15192030, 26720470, 29555955; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs61750065, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1071 of the ABCA4 protein (p.Ser1071Leu). |
DASA | RCV002255094 | SCV002526422 | pathogenic | ABCA4-Related Disorders | 2022-06-10 | criteria provided, single submitter | clinical testing | The c.3212C>T;p.(Ser1071Leu) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 99208; PMID: 29555955; PMID: 26720470) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (AAA_21; ABC_tran) - PM1. The variant is present at low allele frequencies population databases (rs61750065– gnomAD 0.0001314%; ABraOM no frequency - http://abraom.ib.usp.br/) -PM2_supporting. The p.(Ser1071Leu) was detected in trans with a Pathogenic variant (PMID: 26720470) - PM3. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is Pathogenic |
Ophthalmic Genetics Group, |
RCV003324508 | SCV004030376 | pathogenic | Cone-rod dystrophy | 2023-07-24 | criteria provided, single submitter | research | Clinical significance based on ACMG v2.0 |
Retina International | RCV000085559 | SCV000117696 | not provided | not provided | no assertion provided | not provided |