ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.3386G>T (p.Arg1129Leu)

gnomAD frequency: 0.00022  dbSNP: rs1801269
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV000408578 SCV000281868 likely pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763045 SCV000893526 pathogenic Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 2024-06-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000085576 SCV001233046 pathogenic not provided 2025-01-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1129 of the ABCA4 protein (p.Arg1129Leu). This variant is present in population databases (rs1801269, gnomAD 0.2%). This missense change has been observed in individual(s) with Stargardt disease or cone-rod dystrophy (PMID: 19074458, 23755871, 27032803, 29114839). 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: 99224). 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%. 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 RCV001075726 SCV001241354 pathogenic Retinal dystrophy 2019-05-09 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001199211 SCV001370233 pathogenic Age related macular degeneration 2 2019-02-27 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PM5,PP2,PP3,PP5.
GeneDx RCV000085576 SCV001813911 pathogenic not provided 2022-11-04 criteria provided, single submitter clinical testing Reported as a common pathogenic variant among individuals of Spanish background (Riveiro-Alvarez et al., 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28771251, 29114839, 27032803, 30337596, 30093795, 32483926, 32845050, 32036094, 25698705, 17277736, 9295268, 29555955, 28118664, 19074458, 16917483, 30156925, 32141364, 32619608, 31589614, 34327195, 34426522, 33090715, 33302505, 11017087, 23755871, 29925512)
Mendelics RCV001199211 SCV002517485 pathogenic Age related macular degeneration 2 2022-05-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000085576 SCV003812962 pathogenic not provided 2022-04-26 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV001075726 SCV005073617 likely pathogenic Retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Retina International RCV000085576 SCV000117714 not provided not provided no assertion provided not provided
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana RCV000408578 SCV005047005 pathogenic Severe early-childhood-onset retinal dystrophy no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV004732670 SCV005345604 pathogenic ABCA4-related disorder 2024-09-19 no assertion criteria provided clinical testing The ABCA4 c.3386G>T variant is predicted to result in the amino acid substitution p.Arg1129Leu. This variant has been reported to be causative for autosomal recessive retinal disorders and is a prevalent pathogenic variant in Mexican Stargardt disease patients (Bravo-Gil et al. 2016. PubMed ID: 27032803; Riveiro-Alvarez et al. 2007. PubMed ID: 17277736; Riveiro-Alvarez et al. 2013. PubMed ID: 23755871). This variant is reported in 0.17% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.