TABLE 1.

Information about in silico tools for variant analysis categorized by the differential analytic features.

Software	Pathogenicity score	Link	Reference	Citations a
Interspecific and evolutionary sequential conservation
SIFT	<0.05	N/A	Ng et al. (2003)	5,656
Align-GVGD	> C35	http://agvgd.hci.utah.edu/agvgd_input.php	Tavtigian et al. (2006)	678
MAPP	Not tolerated	http://mendel.stanford.edu/sidowlab/downloads/MAPP/	Stone et al. (2005)	404
PhastCons	N/A	http://compgen.bscb.cornell.edu/phast	Siepel et al. (2005)	4,252
PhyloP	N/A	http://compgen.bscb.cornell.edu/phast	Pollard et al. (2010)	2,244
GERP	≥2	http://mendel.stanford.edu/SidowLab/downloads/gerp/	Davydov et al. (2010)	1,524
Mutation Assessor	0.8 < x ≤ 1.9 > low impact	http://mutationassessor.org/r3/	Reva et al. (2011)	1,817
	1.9 < x ≤ 3.5 > medium impact
	<3.5 > high impact
FATHMM	<0	http://fathmm.biocompute.org.uk/	Shihab et al. (2012)	1,044
PROVEAN	−2,282	NA	Choi et al. (2012)	2,781
Panther	Deleterious	http://www.pantherdb.org/about.jsp	Mi et al. (2019)	2,356
Sequence/Structure tools
MutPred	>0.5	http://mutpred.mutdb.org/index.html	Li et al. (2009)	807
SNPeffect	Reduced Stability	http://snpeffect.switchlab.org/	De Beats et al. (2012)	247
PolyPhen-2	Probably damaging (≥0.957)	http://genetics.bwh.harvard.edu/pph2/index.shtml	Adzhubei et al. (2013)	12,463
	Possibly damaging (0.453 ≤ x ≤ 0.956)
Supervised Machine Learning Analysis
VEST	>0.5	https://karchinlab.org/apps/appVest.html	Carter et al. (2013)	389
Mutation Taster	>0.5 (Disease Causing)	http://www.mutationtaster.org/	Schwarz et al. (2014)	3,054
Mutation Taster 2021	Deleterious	https://www.genecas2003cade.org/MutationTaster2021/	Steinhaus et al. (2021)	32
CADD	>20	https://cadd.gs.washington.edu/	Kircher et al. (2014)	5,163
M-CAP	>0.025	http://bejerano.stanford.edu/mcap/	Jagadeesh et al. (2016)	621
REVEL	>0.5	N/A	Ioannidis et al. (2016)	1,109
BayesDel	>0.0692655	http://fengbj-laboratory.org/BayesDel/BayesDel.html	Feng et al. (2017)	75
Unsupervised Machine Learning Analysis
GenoCanyon	>0.5	http://zhaocenter.org/GenoCanyon_Index.html	Lu et al. (2015)	151
Eigen	>0.5	http://www.columbia.edu/∼ii2135/download.html	Ionita-Laza et al. (2016)	483
Splicing analysis
Nnsplice	0.4	https://www.fruitfly.org/seq_tools/splice.html	Reese et al. (1997)	1904
MaxEntScan	N/A	http://hollywood.mit.edu/burgelab/maxent/Xmaxentscan_scoreseq.html	Yeo et al. (2004)	1959
HSF	N/A	https://www.genomnis.com/access-hsf	Desmet et al. (2009)	2,556
dbscSNV	0.6	http://www.liulab.science/dbscsnv.html	Jian et al. (2014)	365
SpliceAI	0.5	https://spliceailookup.broadinstitute.org/	Jaganathan et al. (2019)	826

^a Number of citations according to Google Scholar.