ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.521A>G (p.Tyr174Cys) (rs1557052390)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536329 SCV000630010 pathogenic Adrenoleukodystrophy 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 174 of the ABCD1 protein (p.Tyr174Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with X-linked adrenoleukodystrophy (ALD) (PMID: 10737980, 24722136, 15800013, 15811009) and has reported to segregate with X-linked ALD in a single family (PMID: 11336405). Experimental studies have shown that this missense change affects the cellular localization of the ABCD1 protein (also known as ALDP) (PMID: 17542813). Different missense substitutions at this codon (p.Tyr174Ser, p.Tyr174Asp) have been determined to be pathogenic (PMID: 7860075, 15811009, 7849723). This suggests that the tyrosine residue is critical for ABCD1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000536329 SCV001142048 pathogenic Adrenoleukodystrophy 2019-05-28 criteria provided, single submitter clinical testing

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