ClinVar

Description

The c.1102C>T (p.Gln368Ter) variant is a stop-gained variant. Across a selection of the available literature, the p.Gln368Ter variant has been identified in a heterozygous state in 107 patients affected with primary open angle glaucoma (POAG) or ocular hypertension (Stone et al. 1997; Angius et al. 2000; Craig et al. 2001; Mataftsi et al. 2001; Cobb et al. 2002; Faucher et al. 2002; Melki et al. 2003; Bhattacharjee et al. 2007; Lopez-Martinez et al. 2007; Hogewind et al. 2010; Liu et al. 2012; Young et al. 2012). The p.Gln368Ter variant was also reported in a heterozygous state in 56 controls and unaffected family members and is reported at a frequency of 0.00363 in the European (Finnish) population of the Exome Aggregation Consortium. The relatively high number of unaffected individuals carrying the variant could be consistent with reduced or age-related penetrance. This variant may represent a risk allele for development of POAG. In vitro functional studies by Aroca-Aquilar et al. (2008) showed that heterozygous expression of the p.Gln368Ter variant increases secretion of the variant protein and reduces extracellular processed myocilin, while Qiu et al. (2014) demonstrated that p.Gln368Ter variant myocilin results in compromised ubiquitin-proteasome function and induced autophagy. Based on the evidence, the p.Gln368Ter variant is classified as likely pathogenic and possible risk allele for primary open angle glaucoma.