ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.3064G>A (p.Glu1022Lys) (rs61749459)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408496 SCV000281858 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085545 SCV000511889 likely pathogenic not provided 2016-10-12 criteria provided, single submitter clinical testing The E1022K variant has been published in association with ABCA4-related disorders (Webster et al., 2001; Stone et al., 2003; Stenirri et al., 2004; Fumagalli et al., 2001; Fujinami et al., 2013; Fujinami et al., 2015). The E1022K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E1022K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (T1019A, T1019M, F1026L) have been reported in the Human Gene Mutation Database in association with Stargardt disease (Stenson et al., 2014). Therefore, based on the currently available information, E1022K is likely pathogenic.
Invitae RCV000085545 SCV001218586 pathogenic not provided 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1022 of the ABCA4 protein (p.Glu1022Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs61749459, ExAC 0.006%). This variant has been observed in individual(s) with Stargardt disease (PMID: 11702214, 23982839, 30834176). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99196). 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. For these reasons, this variant has been classified as Pathogenic.
Retina International RCV000085545 SCV000117682 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000408496 SCV000598958 likely pathogenic Stargardt disease 1 2015-01-01 no assertion criteria provided research

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