ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.4462T>C (p.Cys1488Arg) (rs61750146)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408472 SCV000281892 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085637 SCV000321351 pathogenic not provided 2016-10-12 criteria provided, single submitter clinical testing The C1488R pathogenic variant in the ABCA4 gene has been published previously in association with Stargardt disease (Lewis et al., 1999; Briggs et al., 2001; Webster et al., 2001). The 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. C1488R 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. Functional studies have shown that C1488R results in lowered ATPase activity compared to wild type (Sun et al., 2000). Missense variants in the same codon (C1488Y/F) and in nearby residues (P1486L, C1490Y) have been reported in the Human Gene Mutation Database in association with Stargardt disease (Stenson et al., 2014), supporting the functional importance of this region of the protein.
Fulgent Genetics,Fulgent Genetics RCV000763043 SCV000893524 likely pathogenic Cone-rod dystrophy 3; Age-related macular degeneration 2; Stargardt disease 1; Retinitis pigmentosa 19 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000085637 SCV001222273 pathogenic not provided 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 1488 of the ABCA4 protein (p.Cys1488Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs61750146, ExAC 0.003%). This variant has been observed in individual(s) with ABCA4-related conditions (PMID: 29555955, 28559085, 29925512, 22449572). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99284). This variant has been reported to affect ABCA4 protein function (PMID: 11017087). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073630 SCV001239181 pathogenic Retinal dystrophy 2019-07-20 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085637 SCV001248244 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing
Retina International RCV000085637 SCV000117776 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.