Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001882207 | SCV002162943 | uncertain significance | Adrenoleukodystrophy | 2024-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 712 of the ABCD1 protein (p.Arg712His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of ABCD1-related conditions (PMID: 32403196, 35466195). ClinVar contains an entry for this variant (Variation ID: 1392542). 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 not expected to disrupt ABCD1 protein function with a negative predictive value of 95%. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
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, |
RCV001882207 | SCV005077804 | likely pathogenic | Adrenoleukodystrophy | 2024-05-09 | criteria provided, single submitter | clinical testing |