ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.52C>T (p.Arg18Trp)

gnomAD frequency: 0.00005  dbSNP: rs121909205
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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 RCV000008356 SCV000281792 likely pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000085719 SCV000701766 pathogenic not provided 2016-09-28 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075717 SCV001241345 pathogenic Retinal dystrophy 2019-05-09 criteria provided, single submitter clinical testing
Invitae RCV000085719 SCV001402755 pathogenic not provided 2021-11-25 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 18 of the ABCA4 protein (p.Arg18Trp). This variant is present in population databases (rs121909205, gnomAD 0.003%). This missense change has been observed in individuals with Stargardt disease and retinal disease (PMID: 23096905, 23755871, 29854428, 29925512). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7899). 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. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085719 SCV001447330 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000008356 SCV001573651 pathogenic Severe early-childhood-onset retinal dystrophy 2021-04-08 criteria provided, single submitter research The ABCA4 c.52C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM1, PP1, PM3-S. Based on this evidence we have classified this variant as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000085719 SCV001745932 pathogenic not provided 2021-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000085719 SCV001796097 pathogenic not provided 2021-09-22 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 9503029, 28044389, 10090887, 23755871, 28118664, 27014590, 29555955, 30204727, 29925512, 31589614)
OMIM RCV000008356 SCV000028564 pathogenic Severe early-childhood-onset retinal dystrophy 1998-02-15 no assertion criteria provided literature only
Retina International RCV000085719 SCV000117859 not provided not provided no assertion provided not provided

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