Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000085562 | SCV001228211 | pathogenic | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1087 of the ABCA4 protein (p.Glu1087Lys). This variant is present in population databases (rs61751398, gnomAD 0.01%). This missense change has been observed in individual(s) with Stargardt disease, Leber congenital amaurosis, or cone-rod dystrophy (PMID: 9054934, 19265867, 22264887, 28559085, 30576320). 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: 99211). 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%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ABCA4 function (PMID: 11017087). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001075833 | SCV001241472 | pathogenic | Retinal dystrophy | 2019-07-25 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000085562 | SCV001249468 | pathogenic | not provided | 2019-03-01 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV001199228 | SCV001370265 | pathogenic | Age related macular degeneration 2 | 2019-03-17 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PM5,PP2,PP3. This variant was detected in homozygous state. |
Kariminejad - |
RCV001814057 | SCV001755586 | pathogenic | Abnormality of the eye | 2021-07-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000085562 | SCV001804262 | pathogenic | not provided | 2021-11-12 | criteria provided, single submitter | clinical testing | Published functional studies suggest a damaging effect with reduced protein expression and decreased ATPase activity (Sun et al., 2000); 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: 12824224, 22264887, 20128570, 11328725, 11702214, 11017087, 23883535, 9054934, 14709597, 27820952, 32845050, 29925512, 30204727, 32619608, 28559085, 30576320, 19265867) |
3billion | RCV001808323 | SCV002058562 | pathogenic | Retinitis pigmentosa 19 | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000099211, PMID:9054934, PS1_S). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000099212,VCV001068257, PMID:14517951,29925512, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.966, 3CNET: 0.994, PP3_P). A missense variant is a common mechanism associated with Retinitis pigmentosa 19 (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Genetics and Molecular Pathology, |
RCV002466427 | SCV002761865 | pathogenic | Cone-rod dystrophy 3 | 2021-01-20 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002498455 | SCV002813171 | pathogenic | Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 | 2021-09-24 | criteria provided, single submitter | clinical testing | |
Retina International | RCV000085562 | SCV000117699 | not provided | not provided | no assertion provided | not provided |