ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.50G>A (p.Arg17His)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000721078 SCV000851963 likely benign History of neurodevelopmental disorder 2016-10-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Intact protein function observed in appropriate functional assay(s),Other data supporting benign classification
Invitae RCV000707690 SCV000836797 uncertain significance Adrenoleukodystrophy 2018-03-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 17 of the ABCD1 protein (p.Arg17His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual with adult cerebral adrenoleukodystrophy (PMID: 15811009). However, in that individual a pathogenic variant was also identified in ABCD1, which suggests that this c.50G>A variant was not the primary cause of disease. This variant has also been reported in an individual with adrenoleukodystrophy, but this individual had normal very-long-chain fatty acid levels and the variant was inherited from their unaffected mother (PMID: 27067449). Experimental studies have shown that this missense change results in comparable ALDP expression levels and similar peroxisomal beta-oxidation activity when compared to the cell lines expressing the normal ABCD1 allele (PMID: 27067449). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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