ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.220C>T (p.Arg74Trp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003236250 SCV003933932 likely pathogenic Adrenoleukodystrophy 2023-05-04 criteria provided, single submitter clinical testing Variant summary: ABCD1 c.220C>T (p.Arg74Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 126597 control chromosomes. c.220C>T has been reported in the literature in individuals affected with Adrenoleukodystrophy (e.g. Engelen_2014, vandeStadt_2021). ABCD1 protein is absent in these patients. At least one publication reports experimental evidence and showed that this variant caused reduced expression of ABCD1 protein (Zhang_2011). The following publications have been ascertained in the context of this evaluation (PMID: 24480483, 14533738, 21476988, 34946879). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneDx RCV004593245 SCV005081036 likely pathogenic not provided 2023-12-08 criteria provided, single submitter clinical testing Reported previously in three female individuals from the same family including one individual with a gait disorder, sensory disturbance, spasticity, weakness, and pathological reflexes; the other two individuals had no symptoms reported (PMID: 24480483); Published functional studies showed a non-significant difference in peroxismal targeting (PMID: 14533738); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21476988, 34946879, 24480483, 14533738)

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