ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.5113C>T (p.Arg1705Trp)

gnomAD frequency: 0.00001  dbSNP: rs771038310
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779001 SCV000915442 uncertain significance ABCA4-Related Disorders 2017-09-10 criteria provided, single submitter clinical testing The ABCA4 c.5113C>T (p.Arg1705Trp) missense variant has been reported in at least three studies in which it is found in at least two patients in a compound heterozygous state, one of whom was diagnosed with Stargardt disease before age ten and one diagnosed with a retinopathy noted to be consistent with ABCA4-related retinal disease (Ernest et al. 2009; Fujinami et al. 2013; Lambertus et al. 2015). The p.Arg1705Trp variant was absent from 100 controls and is reported at a frequency of 0.00007 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the p.Arg1705Trp variant is classified as a variant of unknown significance but suspicious for pathogenicity for ABCA4-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
CeGaT Center for Human Genetics Tuebingen RCV000994038 SCV001147330 uncertain significance not provided 2021-05-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory, Institute for Ophthalmic Research RCV001199620 SCV001162384 pathogenic Cone-rod dystrophy 2020-01-09 criteria provided, single submitter research
Invitae RCV000994038 SCV001213376 pathogenic not provided 2023-02-09 criteria provided, single submitter clinical testing 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. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1705 of the ABCA4 protein (p.Arg1705Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with Stargardt disease (PMID: 25444351, 32307445; Invitae). ClinVar contains an entry for this variant (Variation ID: 632119). This variant disrupts the p.Arg1705 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17325179, 23419329, 23769331). 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 RCV001074860 SCV001240462 likely pathogenic Retinal dystrophy 2019-07-31 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV002267624 SCV002549831 likely pathogenic Severe early-childhood-onset retinal dystrophy 2022-06-21 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PM3, PM2_SUP, PM5_SUP, PP3, PP4
Institute of Human Genetics, University of Leipzig Medical Center RCV003322616 SCV004027673 likely pathogenic Retinitis pigmentosa 1 2023-07-04 criteria provided, single submitter clinical testing Criteria applied: PM1,PM5,PM2_SUP,PP3,PP4, PS4_MOD

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