ClinVar

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts a region of the POU1F1 protein in which other variant(s) (p.E250*) have been observed in individuals with POU1F1-related conditions (PMID: 32894409). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this premature translational stop signal affects POU1F1 function (PMID: 11297581). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 13610). This premature translational stop signal has been observed in individual(s) with POU1F1-related conditions (PMID: 11297581). This variant is present in population databases (rs587776798, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Glu250Asnfs*2) in the POU1F1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the POU1F1 protein.