Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000078666 | SCV000110525 | pathogenic | not provided | 2013-08-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000078666 | SCV000329047 | pathogenic | not provided | 2023-06-12 | 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: 26766544, 28559085, 29925512, 31429209, 32531858, 33706644, 34315337, 35456422, 33369172, 32037395, 25283059, 15579991, 9973280, 25087612, 11527935, 28341476, 28041643, 19074458, 10396622, 16682602, 30634128, 30204727, 30718709, 11017087, 32467599, 31456290, 32581362, 33375396, 34426522, 31573552, 31589614, 32619608, 27030965, 28947085, 35119454) |
Knight Diagnostic Laboratories, |
RCV000454310 | SCV000538009 | pathogenic | Mandibulofacial dysostosis with mental deficiency | 2015-07-24 | criteria provided, single submitter | clinical testing | This variant has been observed, either as homozygous (Hwang JC et al., 2009) or compound heterozygous (Lewis RA et al., 1999) in individuals who have been diagnosed with Stargardt disease. It co-segregates with disease and was found in trans with the known pathogenic variant, G1961E (Duncker T et al., 2015). In the protein, it is present in the helical transmembrane domain 7 and is close to the nucleotide binding domain-1. Studies in HEK 293 cells showed that, compared with wild-type, the protein yield and ATP-binding capacity of this variant was reduced (Sun H et al., 2000). Finally, multiple computational algorithms predict this variant to be deleterious and its frequency in the population databases (1000 Genomes, Exome Sequencing Project [ESP] and ExAC) is either absent or very low. Therefore, this variant meets our criteria for a Pathogenic classification. We have confirmed this finding in our laboratory using Sanger sequencing. |
Fulgent Genetics, |
RCV000763044 | SCV000893525 | pathogenic | Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 | 2021-10-08 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000778258 | SCV000914430 | pathogenic | ABCA4-Related Disorders | 2018-08-21 | criteria provided, single submitter | clinical testing | The ABCA4 c.4139C>T (p.Pro1380Leu) missense variant has been reported in at least ten studies in which it is found in at least 38 individuals with either Stargardt disease (STGD), cone-rod dystrophy or age related macular degeneration including in five individuals in a homozygous state, at least 29 in a compound heterozygous state, and four individuals in a heterozygou state (Shroyer et al. 1999; Lewis et al. 1999; Shroyer et al. 2001; Briggs et al. 2001; Oh et al. 2004; Fingert et al. 2006; Hwang et al. 2009; Cideciyan et al. 2009; Chacón-Camacho et al. 2013; Duncker et al. 2015). The p.Pro1380Leu variant has been shown to segregate with STGD disease in at least three families (Lewis et al. 1999; Shroyer et al. 2001; Cideciyan et al. 2009). The variant has not been reported in association with retinitis pigmentosa. The p.Pro1380Leu variant was absent from at least 895 controls and is reported at a frequency of 0.001973 in the Ashkenazi Jewish population of the Genome Aggregation Database. In vitro analysis in HEK-293 cells demonstrated that the p.Pro1380Leu variant resulted in reduced expression of the protein and defective ATP binding (Sun et al. 2000). Based on the collective evidence, the p.Pro1380Leu variant is classified as pathogenic for ABCA4-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV000078666 | SCV001211297 | pathogenic | not provided | 2024-01-31 | 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 1380 of the ABCA4 protein (p.Pro1380Leu). This variant is present in population databases (rs61750130, gnomAD 0.2%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 9973280, 28559085). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7904). 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 have shown that this missense change affects ABCA4 function (PMID: 11017087). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001075868 | SCV001241509 | pathogenic | Retinal dystrophy | 2019-08-14 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000078666 | SCV001249460 | pathogenic | not provided | 2019-07-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000078666 | SCV001447241 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Institute of Medical Molecular Genetics, |
RCV000008362 | SCV001548095 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2021-01-30 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000078666 | SCV002020375 | pathogenic | not provided | 2021-06-23 | criteria provided, single submitter | clinical testing | |
Ophthalmic Genetics Group, |
RCV000787498 | SCV004030409 | pathogenic | Stargardt disease | 2023-07-24 | criteria provided, single submitter | research | Clinical significance based on ACMG v2.0 |
OMIM | RCV000008362 | SCV000028570 | pathogenic | Severe early-childhood-onset retinal dystrophy | 2006-05-01 | no assertion criteria provided | literature only | |
OMIM | RCV000023139 | SCV000044430 | risk factor | MACULAR DEGENERATION, AGE-RELATED, 2, SUSCEPTIBILITY TO | 2006-05-01 | no assertion criteria provided | literature only | |
Retina International | RCV000078666 | SCV000117745 | not provided | not provided | no assertion provided | not provided | ||
NIHR Bioresource Rare Diseases, |
RCV000008362 | SCV000598970 | likely pathogenic | Severe early-childhood-onset retinal dystrophy | 2015-01-01 | no assertion criteria provided | research | |
Department of Clinical Genetics, |
RCV000787498 | SCV000926464 | likely pathogenic | Stargardt disease | 2018-04-01 | no assertion criteria provided | research | |
Sharon lab, |
RCV000787498 | SCV001160848 | pathogenic | Stargardt disease | 2019-06-23 | no assertion criteria provided | research | |
Clinical Genetics, |
RCV000078666 | SCV001922450 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000078666 | SCV001951354 | pathogenic | not provided | no assertion criteria provided | clinical testing |