Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003783756 | SCV004571457 | uncertain significance | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 368 of the NR0B1 protein (p.Cys368Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital adrenal hypoplasia (PMID: 20573681). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NR0B1 function (PMID: 20573681). 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. |