ClinVar

Description

Variant summary: CYP1B1 c.431A>G (p.Gln144Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.3e-05 in 184526 control chromosomes. c.431A>G has been reported in the literature as a non-informative genotype (i.e., second allele and/or phase not specified) in individuals with primary open-angle glycoma (POAG), juvenile onset open angle glaucoma (JOAG), primary angle closure (PACG) glaucoma and primary congenital galucoma (PCG) (example, Chakrabarti_2007, Khafagy_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Primary Congenital Glaucoma. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in a severe alteration in RA-metabolism without any comprehensive alteration in estradiol metabolism activity (Bannerjee_2016). Based on this functional outcome, the genotype to phenotype correlation was reported as "PCG (primary congenital glaucoma): Predicted for a homozygote". The following publications have been ascertained in the context of this evaluation (PMID: 27243976, 18055790, 31024815). ClinVar contains an entry for this variant (Variation ID: 1329081). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.