ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu) (rs1557054776)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000727694 SCV000883320 pathogenic not provided 2018-05-16 criteria provided, single submitter clinical testing The ABCD1 c.1628C>T; p.Pro543Leu variant has been described in several individuals affected with adrenoleukodystrophy (ALD) with no detectable level of peroxisomal ABC half-transporter (ALDP) in their cells (see link to ALD ABCD1 database and references therein). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 543 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. Another variant at this codon (c.1627C>T; p.Pro543Ser) has been identified in patients with ALD and is considered pathogenic (see link to ALD ABCD1 database and references therein). Based on available information, the p.Pro543Leu variant is considered pathogenic. References: ALD ABCD1 Database: http://adrenoleukodystrophy.info/mutations-and-variants-in-abcd1
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727694 SCV000855037 pathogenic not provided 2018-05-25 criteria provided, single submitter clinical testing
Invitae RCV000633485 SCV000754718 pathogenic Adrenoleukodystrophy 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 543 of the ABCD1 protein (p.Pro543Leu). 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 reported in several individuals affected with adrenoleukodystrophy (ALD) (PMID: 9242200, 10737980, 10980539, 11748843, 15811009, 24788897). This variant has also been reported in female carrierss affected with late-onset neurological symptoms (PMID: 24480483). Experimental studies have shown that this missense change results in absence of ALD protein (PMID: 11748843, 27067449). For these reasons, this variant has been classified as Pathogenic.

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