Table 1.

Level of evidence for gene mutations

Level	Criteria
Annotation error	When the record is related to a different disease or biological topic (mainly due to imprecisions in the gene and disease systematic annotations)
Unrelated	When the record is properly annotated but the mention of disease or the gene is casual or not the main topic
Negative evidence	When studies test gene polymorphisms and dismiss a relationship with PAH
Biologically related but no evidence of mutation	When the studies performed experiments in non-human specimens or cell cultures showing a biological relationship with PAH, treatment or development of the disease but not evidence of mutations in patients is mentioned
Experimental evidence of mutations	When experimental evidence of mutation is shown in a group of patients
Other evidences of genetic alterations	When not specific gene mutations are provided such as haplotypes or GWAS (genome wide association studies)
Genetic alteration in a related disease	When experimental evidence of mutations is provided not specifically for PAH or PAH is not the main topic