ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1640A>G (p.Tyr547Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005201518 SCV005840569 likely pathogenic Adrenoleukodystrophy 2024-08-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 547 of the ABCD1 protein (p.Tyr547Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with primary adrenal insufficiency and/or X-linked adrenoleukodystrophy (PMID: 23300730, 26523528). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ABCD1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ABCD1 function (PMID: 23300730). 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.

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