Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000635250 | SCV000756636 | likely pathogenic | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2022-06-09 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Leu381Pro amino acid residue in NR0B1. Other variant(s) that disrupt this residue have been observed in individuals with NR0B1-related conditions (PMID: 11113848, 28546232), 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) performed at Invitae indicates that this missense variant is expected to disrupt NR0B1 protein function. ClinVar contains an entry for this variant (Variation ID: 492856). This missense change has been observed in individual(s) with clinical features of congenital adrenal hypoplasia (PMID: 31263616). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 381 of the NR0B1 protein (p.Leu381Pro). |
Clinical Molecular Genetics Laboratory, |
RCV000584385 | SCV000692289 | pathogenic | Congenital adrenal hypoplasia, X-linked | 2008-02-13 | no assertion criteria provided | clinical testing |