ClinVar

Description

Variant summary: CYP1B1 c.319C>G (p.Leu107Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 196756 control chromosomes, predominantly at a frequency of 0.0042 within the East Asian subpopulation in the gnomAD database. This frequency similar to the expected for a pathogenic variant in CYP1B1 causing Primary Congenital Glaucoma (0.00034 vs 0.0043), suggesting the variant might be a polymorphism found in the East Asian population. c.319C>G has been reported in the literature in individuals affected with Primary Congenital Glaucoma without strong evidence for causality, as well as in controls and unaffected individuals (eg. Chen_2008, Kim_2011, Chen_2014, Chen_2015, Gong_2015, Qiao_2021). These reports do not provide unequivocal conclusions about association of the variant with Primary Congenital Glaucoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Three submitters classified the variant as VUS while one classified as benign. Based on the evidence outlined above, the variant was classified as uncertain significance.