Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003797378 | SCV004586473 | uncertain significance | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2023-05-05 | 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. This variant disrupts the p.Leu386 amino acid residue in NR0B1. Other variant(s) that disrupt this residue have been observed in individuals with NR0B1-related conditions (PMID: 21029627, 30620004, 32482417), which suggests that this may be a clinically significant amino acid residue. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NR0B1 protein function. This variant has not been reported in the literature in individuals affected with NR0B1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 386 of the NR0B1 protein (p.Leu386Arg). |