Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000710404 | SCV000840616 | uncertain significance | not provided | 2019-05-10 | criteria provided, single submitter | clinical testing | |
Johns Hopkins Genomics, |
RCV000787041 | SCV000925956 | likely pathogenic | Adrenoleukodystrophy | 2019-03-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000787041 | SCV000951341 | likely pathogenic | Adrenoleukodystrophy | 2018-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 218 of the ABCD1 protein (p.Pro218Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Pro218 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 10737980, 17372139), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individuals affected with adrenoleukodystrophy (Invitae, https://adrenoleukodystrophy.info/mutations-and-variants-in-abcd1). This variant is not present in population databases (ExAC no frequency). |
Genome- |
RCV000787041 | SCV002045725 | uncertain significance | Adrenoleukodystrophy | 2021-11-07 | criteria provided, single submitter | clinical testing | |
3billion | RCV000787041 | SCV002521754 | uncertain significance | Adrenoleukodystrophy | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.96). Different missense changes at the same codon (p.Pro218Ser, p.Pro218Thr) have been reported to be associated with ABCD1- related disorder (PMID: 10737980, 22280810). However the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. |