ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1957C>T (p.Arg653Cys) (rs61749420)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408546 SCV000281839 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085452 SCV000574771 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763047 SCV000893528 likely pathogenic Cone-rod dystrophy 3; Age-related macular degeneration 2; Stargardt disease 1; Retinitis pigmentosa 19 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000085452 SCV001202188 pathogenic not provided 2020-09-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 653 of the ABCA4 protein (p.Arg653Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs61749420, ExAC 0.002%). This variant has been observed in several individuals affected with Stargardt disease, and was observed to segregate with cone rod dystrophy in a family (PMID: 28559085, 23776498). ClinVar contains an entry for this variant (Variation ID: 99108). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg653 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9466990, 10413692, 19074458). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074668 SCV001240260 pathogenic Retinal dystrophy 2019-03-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085452 SCV001446861 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV000408546 SCV001548139 likely pathogenic Stargardt disease 1 2021-01-30 criteria provided, single submitter clinical testing
GeneDx RCV000085452 SCV001782833 pathogenic not provided 2021-08-11 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33375396, 10958763, 33301772, 28559085, 23776498, 29925512, 32619608, 30204727, 23982839, 18652558, 25444351, 25097154, 23953153, 19265867, 15192030, 28355279, 27939946, 23499370, 11702214, 26957898, 26992781)
Retina International RCV000085452 SCV000117589 not provided not provided no assertion provided not provided
Human Genetics - Radboudumc,Radboudumc RCV000085452 SCV001957874 likely pathogenic not provided no assertion criteria provided clinical testing

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