ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.851C>T (p.Ser284Leu)

dbSNP: rs2091711722
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Goettingen RCV001260592 SCV001397587 likely pathogenic Adrenoleukodystrophy 2020-07-13 criteria provided, single submitter clinical testing The variant c.851C>T (p.(Ser284Leu)) in exon 1 of the ABCD1-gene is not found in known databases (ExAC or gnomAD), it affects a highly conserved nucleotide, a highly conserved amino acid and there is a large physicochemical difference between Ser and Leu. This variant is located in a mutational hotspot and within a protein domain and has a pathogenic computational verdict based on 8 pathogenic predictions from DANN, DEOGEN2, FATHMM-MKL, M-CAP, MVP, MutationTaster, REVEL and PolyPhen-2 vs 2 benign predictions from MutationAssessor and SIFT. Our male patient, carrying this mutation showed increased plasma levels of very long chain fatty acids (VLCFAs) and a phenotype typical for the adult form of X-linked adrenoleukodystrophy. Thus we consider this ABCD1-variant to be likely pathogenic. ACMG criteria used for classification: PM1, PM2, PP2, PP3, PP4.
MGZ Medical Genetics Center RCV001260592 SCV002580814 likely pathogenic Adrenoleukodystrophy 2022-02-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001260592 SCV003471423 pathogenic Adrenoleukodystrophy 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 284 of the ABCD1 protein (p.Ser284Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with adrenoleukodystrophy (PMID: 35466195, internal data). ClinVar contains an entry for this variant (Variation ID: 981244). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ABCD1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV003135895 SCV003824431 uncertain significance not provided 2022-02-17 criteria provided, single submitter clinical testing

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