Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000439383 | SCV000511884 | likely pathogenic | not provided | 2021-11-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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: 20647261, 29925512) |
Blueprint Genetics | RCV001073702 | SCV001239261 | likely pathogenic | Retinal dystrophy | 2017-04-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000439383 | SCV002266620 | pathogenic | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 640 of the ABCA4 protein (p.Pro640Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive inherited retinal dystrophy (PMID: 20647261, 29925512; Invitae). ClinVar contains an entry for this variant (Variation ID: 377403). 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. |