Table 1.

In silico pathogenicity prediction of the ERCC4;p.Arg726Cys variant.

Software	Score	Prediction
SIFT v6.2.1	0	deleterious
Polyphen-2	1	probably damaging
CADD 1.7	28	moderate pathogenic
REVEL v1.3	0.774	likely disease-causing
MetaLR v0.14.7	0.584	damaging
Mutation Assessor v4	0.965	high pathogenic
AlphaMissense v2.0	0.968	deleterious
Protein stability	ΔΔG (kcal/mol)
MUpro v1.0	−0.883	destabilizing
MAESTROweb v1.2.35	0.184	neutral
DynaMut v2	−0.97	destabilizing
DDGun v2	−1.3	destabilizing
mCSM	−1.907	destabilizing
CUPSAT	−1.68	destabilizing

The pathogenicity prediction follows the guidelines established by the authors. In the protein stability analysis, a negative ΔΔG indicates a decrease in protein stability, with values below −0.5 kcal/mol considered to be significantly destabilizing. Software links: SIFT (https://sift.bii.a-star.edu.sg/), Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/), CADD (https://cadd.gs.washington.edu/), REVEL (https://sites.google.com/site/revelgenomics/), MetaLR (https://github.com/cnodes/metalr/), Mutation Assessor (http://database.liulab.science/dbNSFP), AlphaMissense (https://alphamissense.hegelab.org/search), MUpro (https://mupro.proteomics.ics.uci.edu), MAESTROweb (https://pbwww.services.came.sbg.ac.at/maestro/web/maestro), DynaMut2 (https://biosig.lab.uq.edu.au/dynamut2/), DDGun (https://folding.biofold.org/ddgun/), mCSM (https://biosig.lab.uq.edu.au/mcsm/), CUPSAT(https://cupsat.brenda-enzymes.org/).