ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1978C>T (p.Arg660Trp) (rs1569541203)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health: University of Minnesota RCV000710056 SCV000840438 pathogenic Adrenoleukodystrophy 2017-10-24 criteria provided, single submitter clinical testing
Invitae RCV000710056 SCV000965551 pathogenic Adrenoleukodystrophy 2019-03-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 660 of the ABCD1 protein (p.Arg660Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with adrenoleukodystrophy or adrenomyeloneuropathy (PMID: 7825602, 10227685, 15811009, 20661612, 12175782, 8892025, 23835273, 7581394) and reported to segregate with disease in a family (PMID: 24480483). Experimental studies have shown that this missense change disrupts ABCD1 enzymatic activity (PMID: 9051655). This variant disrupts the p.Arg660 amino acid residue in ABCD1. Other variants that disrupt this residue have been observed in affected individuals (PMID: 21966424, 11438993, 21889498), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics,Johns Hopkins University RCV000710056 SCV001425349 pathogenic Adrenoleukodystrophy 2020-03-10 criteria provided, single submitter clinical testing

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.