ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.6112C>T (p.Arg2038Trp)

gnomAD frequency: 0.00004  dbSNP: rs61750643
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV000408458 SCV000281949 pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073850 SCV001239414 pathogenic Retinal dystrophy 2018-07-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000085789 SCV001402865 pathogenic not provided 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2038 of the ABCA4 protein (p.Arg2038Trp). This variant is present in population databases (rs61750643, gnomAD 0.007%). This missense change has been observed in individuals with Stargardt disease (PMID: 15161829, 24763286, 29854428, 29925512). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99430). 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: 12962493). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085789 SCV001447777 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneDx RCV000085789 SCV001768476 pathogenic not provided 2022-02-21 criteria provided, single submitter clinical testing Published functional studies demonstrate that the p.(R2038W) variant results in decreased ATP hydrolysis and decreased binding affinity for ATP (Biswas-Fiss et al., 2003); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 9054934, 11379881, 15161829, 24763286, 28118664, 31054281, 29555955, 29854428, 33261146, 33090715, 31510083, 22328824, 22863181, 19230850, 9973280, 30093795, 12962493, 29925512)
Retina International RCV000085789 SCV000117931 not provided not provided no assertion provided not provided

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