ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.653C>T (p.Pro218Leu) (rs1569540710)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000710404 SCV000840616 uncertain significance not provided 2018-03-07 criteria provided, single submitter clinical testing
Invitae RCV000787041 SCV000951341 likely pathogenic Adrenoleukodystrophy 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 218 of the ABCD1 protein (p.Pro218Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with adrenoleukodystrophy (Invitae, https://adrenoleukodystrophy.info/mutations-and-variants-in-abcd1). 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.Pro218 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 10737980, 17372139), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Johns Hopkins Genomics,Johns Hopkins University RCV000787041 SCV000925956 likely pathogenic Adrenoleukodystrophy 2019-03-28 criteria provided, single submitter clinical testing

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