ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1165C>T (p.Arg389Cys) (rs128624215)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health: University of Minnesota RCV000761215 SCV000891169 likely pathogenic Adrenoleukodystrophy 2018-04-17 criteria provided, single submitter clinical testing
Invitae RCV000761215 SCV001418216 uncertain significance Adrenoleukodystrophy 2019-06-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 389 of the ABCD1 protein (p.Arg389Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with adrenoleukodystrophy as well as in an individual with hereditary spastic paraplegia (PMID: 15800013, 22280810, 30564185). ClinVar contains an entry for this variant (Variation ID: 623115). 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.Arg389 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8566952, 7825602, 16401743). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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