Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001210777 | SCV001382282 | uncertain significance | Methylmalonic acidemia with homocystinuria, type cblJ | 2023-08-10 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt ABCD4 protein function. ClinVar contains an entry for this variant (Variation ID: 941066). This variant has not been reported in the literature in individuals affected with ABCD4-related conditions. This variant is present in population databases (rs761053363, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 243 of the ABCD4 protein (p.His243Tyr). |