ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.4919G>A (p.Arg1640Gln)

gnomAD frequency: 0.00001  dbSNP: rs61751403
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000321118 SCV000281908 pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000085684 SCV000336550 pathogenic not provided 2015-10-27 criteria provided, single submitter clinical testing
GeneDx RCV000085684 SCV000511902 pathogenic not provided 2021-12-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate that the c.4919 G>A variant may have a negative effect on proper splicing (Schulz et al., 2017); This variant is associated with the following publications: (PMID: 26743751, 11527935, 11379881, 10711710, 23755871, 26377081, 26103963, 25082885, 19074458, 28118664, 28041643, 29925512, 31736247, 31456290, 30718709, 32581362, 31589614, 32037395)
Invitae RCV000085684 SCV001198188 pathogenic not provided 2021-12-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1640 of the ABCA4 protein (p.Arg1640Gln). This variant is present in population databases (rs61751403, gnomAD 0.009%). This missense change has been observed in individuals with Stargardt disease or cone-rod dystrophy (PMID: 10711710, 11527935, 23755871, 26103963). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99331). 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. Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 28118664). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000504816 SCV001239057 pathogenic Retinal dystrophy 2019-04-25 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000085684 SCV001334599 pathogenic not provided 2020-02-01 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV000321118 SCV001548083 likely pathogenic Severe early-childhood-onset retinal dystrophy 2021-01-30 criteria provided, single submitter clinical testing
Retina International RCV000085684 SCV000117824 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504816 SCV000598987 uncertain significance Retinal dystrophy 2015-01-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787505 SCV000926471 pathogenic Stargardt disease 2018-04-01 no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV000787505 SCV001160838 pathogenic Stargardt disease 2019-06-23 no assertion criteria provided research

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