Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001236051 | SCV001408763 | uncertain significance | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2019-09-02 | criteria provided, single submitter | clinical testing | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.Leu262 amino acid residue in NR0B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18339285, 20573681). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been observed in an individual with congenital adrenal hypoplasia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 262 of the NR0B1 protein (p.Leu262Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. |