ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.521A>C (p.Tyr174Ser) (rs1557052390)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV000850177 SCV000992372 likely pathogenic Adrenoleukodystrophy 2019-06-04 criteria provided, single submitter clinical testing
Invitae RCV000850177 SCV001220972 pathogenic Adrenoleukodystrophy 2020-01-19 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with serine at codon 174 of the ABCD1 protein (p.Tyr174Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with X-linked adrenoleukodystrophy (PMID: 7860075, 15811009, 21907609, 28456143). In at least one individual the data is consistent with the variant being de novo. 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.Tyr174 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10737980, 24722136, 15800013, 15811009). 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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