ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1661G>A (p.Arg554His)

dbSNP: rs201568579
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000516866 SCV000202106 pathogenic not provided 2014-02-21 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000516866 SCV000612231 pathogenic not provided 2016-12-13 criteria provided, single submitter clinical testing
Invitae RCV001203306 SCV001374463 pathogenic Adrenoleukodystrophy 2023-08-10 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 554 of the ABCD1 protein (p.Arg554His). This missense change has been observed in individual(s) with adrenoleukodystrophy (PMID: 9242200, 10227685, 23664929, 24719134, 26260157). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 166625). 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 ABCD1 protein function. For these reasons, this variant has been classified as Pathogenic.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris RCV001203306 SCV001519090 pathogenic Adrenoleukodystrophy 2021-01-04 criteria provided, single submitter research
Revvity Omics, Revvity RCV000516866 SCV002019394 pathogenic not provided 2022-06-23 criteria provided, single submitter clinical testing
GeneDx RCV000516866 SCV002044031 pathogenic not provided 2021-12-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15800013, 17504626, 16087056, 9242200, 10227685, 28919002, 26260157, 10737980, 11748843, 14767898, 21068741, 21476988, 22176151, 16415970, 30902905, 23664929, 15811009, 15643618, 23566833, 20859061, 34069712, 31405945, 24719134, 22479560, 32003821)
Genome-Nilou Lab RCV001203306 SCV002045836 pathogenic Adrenoleukodystrophy 2021-11-07 criteria provided, single submitter clinical testing
Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand RCV001203306 SCV004034121 pathogenic Adrenoleukodystrophy 2023-07-01 criteria provided, single submitter research
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV001203306 SCV004046981 pathogenic Adrenoleukodystrophy criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 554 of the ABCD1 protein (p.Arg554His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant has been observed in unrelated individuals and to segregate with adrenoleukodystrophy in a family (Jiang MY et al, Park HJ et al, Zhan ZX et al). The amino acid Arg at position 554 is changed to a His changing protein sequence and it might alter its composition and physico-chemical properties. This variant has been reported to the ClinVar database as Pathogenic. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Arg554His in ABCD1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The p.Arg554His variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant is not present in population databases (ExAC no frequency).For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001203306 SCV004206247 pathogenic Adrenoleukodystrophy 2023-09-21 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000516866 SCV000800835 pathogenic not provided 2015-12-16 no assertion criteria provided clinical testing

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