Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000085466 | SCV001494065 | pathogenic | not provided | 2024-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 75 of the ABCA4 protein (p.Cys75Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with ABCA4-related conditions (PMID: 9973280, 23982839, 30093795). ClinVar contains an entry for this variant (Variation ID: 99122). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782054 | SCV005394686 | pathogenic | Retinitis pigmentosa | 2024-09-24 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.223T>G (p.Cys75Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251414 control chromosomes. c.223T>G has been reported in the literature as a biallelic genotype in multiple individuals affected with features of Autosomal Recessive ABCA4-related disorders (example, Lewis_1999, Fujinami_2013, Salles_2018, Mena_2021, Webster_2001). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23982839, 9973280, 33841504, 30093795, 11328725). ClinVar contains an entry for this variant (Variation ID: 99122). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Retina International | RCV000085466 | SCV000117603 | not provided | not provided | no assertion provided | not provided | ||
| NIHR Bioresource Rare Diseases, |
RCV000504688 | SCV000598949 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2015-01-01 | no assertion criteria provided | research |