Submissions for variant NM_000475.5(NR0B1):c.890T>C (p.Leu297Pro)

dbSNP: rs104894907

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003764556	SCV004571511	uncertain significance	Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2	2023-02-09	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 297 of the NR0B1 protein (p.Leu297Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of X-linked congenital adrenal hypoplasia (PMID: 12629128; Invitae). ClinVar contains an entry for this variant (Variation ID: 10976). 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. Experimental studies have shown that this missense change affects NR0B1 function (PMID: 12629128). 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.
OMIM	RCV000011723	SCV000031955	pathogenic	Congenital adrenal hypoplasia, X-linked	2003-03-01	no assertion criteria provided	literature only
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000011723	SCV000692286	pathogenic	Congenital adrenal hypoplasia, X-linked	2010-02-27	no assertion criteria provided	clinical testing