ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1201C>T (p.Arg401Trp) (rs727503786)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000578153 SCV000680028 pathogenic Adrenoleukodystrophy 2017-09-13 criteria provided, single submitter clinical testing A hemizygous missense variant, NM_000033.3(ABCD1):c.1201C>T, has been identified in exon 3 of 10 in ABCD1. This substitution creates a major amino acid change from an arginine to a tryptophan at position 401, NP_000024.2(ABCD1):p.(Arg401Trp). The arginine residue at this position has very high conservation (100 vertebrates, UCSC), but is not located within a well established functional domain. In-silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G), but has been previously described as pathogenic in multiple families with adrenoleukodystrophy (Takano et al., (1999), Lachtermacher et al., (2000), Vorgerd et al., (1998), Miyoshi et al., (2010), Shimozawa et al., (2011), Pereira et al., (2012)). In addition, two different variants in the same codon resulting in two alternate amino acid changes, have also been shown to cause adrenoleukodystrophy (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
Mendelics RCV000578153 SCV001142053 pathogenic Adrenoleukodystrophy 2019-05-28 criteria provided, single submitter clinical testing

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