ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1979G>A (p.Arg660Gln) (rs1557055340)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000778893 SCV000915296 likely pathogenic Adrenoleukodystrophy 2017-10-20 criteria provided, single submitter clinical testing The ABCD1 c.1979G>A (p.Arg660Gln) missense variant has been reported in at least two studies and is found in a hemizygous state in a total of three individuals with adrenoleukodystrophy (Kumar et al. 2011; Shukla et al. 2011). All three individuals had high plasma very-long-chain fatty acids and onset of symptoms before age five. The p.Arg660Gln variant was absent from 120 controls and is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database. Based on the evidence, the p.Arg660Gln variant is classified as a likely pathogenic for X-linked adrenoleukodystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000778893 SCV001583671 pathogenic Adrenoleukodystrophy 2020-07-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 660 of the ABCD1 protein (p.Arg660Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 21889498, 21966424). ClinVar contains an entry for this variant (Variation ID: 632051). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Arg660 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7825602, 24480483, 9051655). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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