ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1597A>C (p.Lys533Gln) (rs781862879)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000761217 SCV000891171 likely pathogenic Adrenoleukodystrophy 2017-08-16 criteria provided, single submitter clinical testing
Invitae RCV000761217 SCV001588544 pathogenic Adrenoleukodystrophy 2020-05-25 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 533 of the ABCD1 protein (p.Lys533Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is present in population databases (rs781862879, ExAC 0.002%). This variant has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 31074578, 11748843, The ALD Mutation Database). ClinVar contains an entry for this variant (Variation ID: 623117). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Lys533 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in individuals with ABCD1-related conditions (PMID: 15811009, 28991658, Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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