ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.2135G>A (p.Arg712His)

dbSNP: rs1557055447
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001882207 SCV002162943 uncertain significance Adrenoleukodystrophy 2020-08-23 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ABCD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 712 of the ABCD1 protein (p.Arg712His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001882207 SCV005039243 likely pathogenic Adrenoleukodystrophy 2024-03-22 criteria provided, single submitter clinical testing Variant summary: ABCD1 c.2135G>A (p.Arg712His) 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 136350 control chromosomes. c.2135G>A has been reported in the literature in individuals affected with Adrenoleukodystrophy (Priestley_2022, Bibi_2020) and appears to segregate with disease. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32403196, 35466195). ClinVar contains an entry for this variant (Variation ID: 1392542). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV001882207 SCV005077804 likely pathogenic Adrenoleukodystrophy 2024-05-09 criteria provided, single submitter clinical testing

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