Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003064682 | SCV003444439 | uncertain significance | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2022-09-06 | 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.Ala300 amino acid residue in NR0B1. Other variant(s) that disrupt this residue have been observed in individuals with NR0B1-related conditions (PMID: 11443184), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects NR0B1 function (PMID: 11443184). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individuals with X-linked congenital adrenal hypoplasia (PMID: 9063431; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 300 of the NR0B1 protein (p.Ala300Val). |