ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.838C>T (p.Arg280Cys) (rs193922098)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000721083 SCV000851969 pathogenic History of neurodevelopmental disorder 2013-06-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000029290 SCV000051936 likely pathogenic Adrenoleukodystrophy 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Invitae RCV000029290 SCV000948152 pathogenic Adrenoleukodystrophy 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 280 of the ABCD1 protein (p.Arg280Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs193922098, ExAC 0.03%). This variant has been observed in individuals affected with X-linked adrenoleukodystrophy (PMID: 15811009, 11748843, Invitae, https://adrenoleukodystrophy.info/mutations-and-variants-in-abcd1). ClinVar contains an entry for this variant (Variation ID: 35643). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg280 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 11798073), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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