ClinVar

Description

The CYP11B1 c.346T>G (p.Trp116Gly) variant is a missense variant that has been reported in a compound heterozygous state with a second missense variant in one individual with classic CYP11B1 deficiency (Parajes et al. 2010). Control data are not available for the p.Trp116Gly variant, which is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium. However, this frequency is based on one allele only in an area of good sequence coverage, so the variant is presumed to be rare. The Trp116 residue is noted to be conserved in the CYP11 family of proteins and is located in a region of the protein known to control access to the active site of the enzyme. The p.Trp116Gly variant is thought to affect substrate recognition. Expression of the p.Trp116Gly variant in COS-7 cells demonstrated an absence of enzymatic activity (Parajes et al. 2010). Two additional known pathogenic variants affect residue Trp116, p.Trp116Ter and p.Trp116Cys. Based on the evidence, the p.Trp116Gly variant is classified as a variant of unknown significance but suspicious for pathogenicity for congenital adrenal hyperplasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.