Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000132592 | SCV000490382 | likely pathogenic | not provided | 2023-07-23 | criteria provided, single submitter | clinical testing | 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: 25066811, 31054281, 22449572, 26780318, 25474345, 28890726, 29343940, 31589614, 32531858, 34721897, 33301772, 35657619, 33261146, 34758253) |
Mendelics | RCV000986347 | SCV001135325 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2020-01-31 | criteria provided, single submitter | clinical testing | |
Blueprint Genetics | RCV001073482 | SCV001239025 | pathogenic | Retinal dystrophy | 2019-03-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000132592 | SCV001374374 | pathogenic | not provided | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2040 of the ABCA4 protein (p.Arg2040Gln). This variant is present in population databases (rs148460146, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individuals with Stargardt disease (PMID: 22449572, 25066811, 25474345, 26780318). ClinVar contains an entry for this variant (Variation ID: 143076). 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. |
3billion | RCV000986347 | SCV002521807 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.031%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.91; 3Cnet: 0.73). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000143076). A different missense change at the same codon (p.Arg2040Pro) has been reported to be associated with ABCA4 related disorder (ClinVar ID: VCV000806157). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
Dept Of Ophthalmology, |
RCV001073482 | SCV004706425 | likely pathogenic | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
Department of Ophthalmology and Visual Sciences Kyoto University | RCV000132592 | SCV000172537 | probable-non-pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Likely benign. | |
Genomics England Pilot Project, |
RCV001542554 | SCV001760042 | likely pathogenic | Retinitis pigmentosa 19 | no assertion criteria provided | clinical testing |