Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001247760 | SCV001421201 | uncertain significance | Methylmalonic acidemia with homocystinuria, type cblJ | 2022-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 340 of the ABCD4 protein (p.Tyr340Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ABCD4-related conditions. ClinVar contains an entry for this variant (Variation ID: 971876). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCD4 protein function. 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. |