Table 1.

The point system used to score available evidence and to calculate the three individual scores (Association Score, Variant Score and Experimental Score) involved in the calculation of IthaScore. The point system was based on a similar approach described in References [40,46].

	Evidence	Type	Description	Points
Association Score (AS)	Association study	p value	<0.05	0.5
			<0.001	1
			<0.00001	1.5
	Maximum Allowable Sum of Points for Association Score			8
Variant Score (VS)	Genetic variants	Number of variants	One point for each variant in every phenotype stored in IthaGenes.	1
	Maximum Allowable Sum of Points for Variant Score			20
Experimental Score (ES)	Function	Biochemical Function	Functions are shared between gene products involved in the same disease phenotype.	1
		Protein Interaction	Gene product interacts with proteins previously implicated in the disease phenotype. Gene defect disrupting protein interactions.	1
		Expression	Gene is expressed in tissues relevant to the disease phenotype. Altered gene expression in patients.	1
	Functional Alteration	Cells from affected individual	Function of gene product is altered in individuals/engineered cells with candidate mutations (altered expression levels, splicing or normal biochemical function).	1.5
		Engineered cells		1.5
	Model Systems	Animal model	Introduction of the variant or an engineered gene product carrying the variant in a non-human animal model/cell-culture model displays the disease phenotype.	2
		Cell culture model system		2
	Rescue	Rescue in non-human model organism	Addition of the wild-type gene product or specific knockdown of the variant allele can rescue the disease phenotype in a non-human model organism/cell-culture model/patient.	2
		Rescue in cell culture model		2
		Rescue in patients		2
	Maximum Allowable Sum of Points for Experimental Score			6