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: 9
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 2022-02-03 criteria provided, single submitter clinical testing
Invitae RCV000085576 SCV001233046 pathogenic not provided 2024-01-24 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). 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 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
Retina International RCV000085576 SCV000117714 not provided not provided no assertion provided not provided

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.