PFN1 mutations have been reported to be a rare cause of familial ALS.4, 7 The PFN1 E117G variant has been also found in sporadic ALS patients, but its presence in numerous control individuals has raised concerns about its role in disease.4–11 With the recent advances in DNA sequencing technologies, information on one patient's whole exome or multiple candidate genes is quickly obtainable—in this context, the interpretation of variants, such as PFN1 E117G, becomes an important clinical-genetics challenge. The gene discussed is PFN1; the disease is amyotrophic lateral sclerosis.