Table 1.

Main tools for variant interpretation.

Tools for Variant Interpretation	Description	Examples
Databases of genomic variants	They report gene variants with information on their clinical involvement or bibliographic sources in which they are mentioned.	ClinVar, dbSNP 1, HGMD 2, LOVD 3, DGV 4, or LitVar
Predictive programs or in silico studies	These programs include the importance of the alteration both at the nucleotide level and at the amino acid level. They are divided in two groups: (1) prediction whether the change is detrimental to the function or structure of the resulting protein, and (2) prediction if splicing is altered.	PolyPhen2, SIFT, Alamut, or Mutation Taster GeneSplicer, Human Splice Finder, Alamut, REVEL 5 CADD 6, or varSEAK
Evaluation of the frequency of the variant in the control population	Databases of exome and genome sequencing data from a wide variety of large-scale sequencing projects. These databases describe and analyze human genetic variation.	gnomAD 7, 1000 Genomes, or ESP 8
Decision support software	These tools integrate information from several databases and combine it to carry out a classification according to the 2015 ACMG/AMP clinical guidelines	Franklin or Varsome

¹ Single Nucleotide Polymorphism Database, ² Human Gene Mutation Database, ³ Leiden Open Variation Database, ⁴ Data Base of Genomic Variants, ⁵ Rare Exome Variant Ensemble Learner, ⁶ Combined Annotation Dependent Depletion Exome, ⁷ Genome Aggregation Database; ⁸ Exome Sequencing Project.