Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000085848 | SCV000780280 | uncertain significance | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001075235 | SCV001240849 | uncertain significance | Retinal dystrophy | 2017-03-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000085848 | SCV001408552 | pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2241 of the ABCA4 protein (p.Leu2241Val). This variant is present in population databases (rs61748521, gnomAD 0.02%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 29925512; Invitae). ClinVar contains an entry for this variant (Variation ID: 99487). 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. |
| Ophthalmic Genetics Group, |
RCV003324515 | SCV004030357 | likely pathogenic | Stargardt disease | 2023-07-24 | criteria provided, single submitter | research | Clinical significance based on ACMG v2.0 |
| Victorian Clinical Genetics Services, |
RCV004786366 | SCV005399025 | pathogenic | Severe early-childhood-onset retinal dystrophy | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Stargardt disease 1 (MIM#248200) and other inherited retinal diseases (OMIM). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 31522899). (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to valine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (29 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic and pathogenic by clinical laboratories in ClinVar, as well as older VUS entries. This variant has also been observed in multiple unrelated compound heterozygous individuals with Stargardt disease or macular dystrophy (PMID: 29925512, 35156991, 35260635), including as part of the complex allele p.(Leu2241Val);p.(Asn1868Ile) in three unrelated individuals (PMID: 32307445, 38003421, 36909829). (SP) 1207 - Parental origin of the variant is unresolved (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Retina International | RCV000085848 | SCV000117991 | not provided | not provided | no assertion provided | not provided |