Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000824100 | SCV000964982 | likely pathogenic | Adrenoleukodystrophy | 2021-06-01 | criteria provided, single submitter | clinical testing | 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. The observation of additional missense substitutions at this codon (p.Gly298Asp and p.Gly298Arg) in affected individuals suggests that this may be a clinically significant residue (PMID: 10480364, 26454440). 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 several individuals affected with ABCD1-related conditions (PMID: 10737980, Invitae). ClinVar contains an entry for this variant (Variation ID: 665751). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 298 of the ABCD1 protein (p.Gly298Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |
Genome- |
RCV000824100 | SCV002045762 | likely pathogenic | Adrenoleukodystrophy | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Johns Hopkins Genomics, |
RCV000824100 | SCV000992377 | uncertain significance | Adrenoleukodystrophy | 2019-06-10 | flagged submission | clinical testing |