Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001204546 | SCV001375757 | pathogenic | Adrenoleukodystrophy | 2019-09-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys631 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in individuals with ABCD1-related conditions (PMID: 15811009), which suggests that this may be a clinically significant amino acid residue. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with adrenoleukodystrophy (PMID: 18973459, Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 631 of the ABCD1 protein (p.Cys631Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |