ClinVar

Description

Variant summary: CYP1B1 c.343G>C (p.Ala115Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1e-05 in 200844 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.343G>C has been reported in the literature in homozygous individuals affected with Primary Congenital Glaucoma (example: Reddy_2004 and Sheikh_2014), however in one these families the variant was also observed in five homozygous clinically normal individuals (Sheikh_2014). Since the penetrance of Primary Congenital Glaucoma (0.44) due to this variant appears to be lower than expected (0.8), no conclusions can be drawn from these data. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.