ClinVar

Description

Variant summary: PROP1 c.550G>C (p.Ala184Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.8e-05 in 249674 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in PROP1 causing Combined Pituitary Hormone Deficiency (6.8e-05 vs 0.0041), allowing no conclusion about variant significance. c.550G>C has been reported in the literature in individuals affected with Combined Pituitary Hormone Deficiency (Blum_2018) without strong evidence for causality. This report does not provide unequivocal conclusions about association of the variant with Combined Pituitary Hormone Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.