Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001870205 | SCV002127200 | uncertain significance | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2021-02-28 | criteria provided, single submitter | clinical testing | 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 NR0B1 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. This variant has not been reported in the literature in individuals with NR0B1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with glycine at codon 269 of the NR0B1 protein (p.Val269Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. |