ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1895C>T (p.Thr632Ile) (rs1064793877)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480881 SCV000567248 pathogenic not provided 2016-03-02 criteria provided, single submitter clinical testing The T632I pathogenic variant in the ABCD1 gene has been reported previously in associationwith X-linked adrenoleukodystrophy (ALD) in a large family with several affected males withphenotypes ranging from isolated Addison disease to juvenile cerebral ALD (Jorge et al., 1996).The T632I variant was not observed in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. The T632I variant is a non-conservative amino acid substitution,which is likely to impact secondary protein structure as these residues differ in polarity, charge,size and/or other properties. This substitution occurs at a position that is conserved acrossspecies, and in silico analysis predicts this variant is probably damaging to the proteinstructure/function. Furthermore, a missense variant at the same residue (T632P) and in in nearbyresidues (L628Q/P, D629H/N, E630K/G, C631R/Y/W, S633I/R, V635M, S636I) have beenreported in the Human Gene Mutation Database in association with ALD (Stenson et al., 2014),supporting the functional importance of this region of the protein. Therefore, we interpret T632Ito be a pathogenic variant.
Johns Hopkins Genomics,Johns Hopkins University RCV000853230 SCV000996046 pathogenic Adrenoleukodystrophy 2019-07-31 criteria provided, single submitter clinical testing

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