Table 1.

Variant filtering and analysis scheme.

Step	Number of variants
Trio exome sequencing	111,596
Annotation and filtering with Ensembl VEP
Filter 1: AF <2 % in population subcohorts, <5 x homozygous occurrences in gnomAD exomes v2.1.1	7,031
Filter 2: VEP impact HIGH or MODERATE or SpliceAI score >0.1	841
Prioritization
1) Variants in candidate genes of phenotypic relevance	92
2) Variants segregating in compliance with a Mendelian Disease (full penetrance)	65
Variants shared between (1) and (2) (these variants can be found in Supplementary Data 1)	7 (genes: TTN (2x), DNM1L, TBK1, TNFRSF13B, and RUNX1 (2x))
Variants considered relevant to the severe COVID-19 disease course	2 (genes: TBK1 and TNFRSF13B)

Note that gene symbols are italicized.

COVID-19 coronavirus disease, VEP variant effect predictor, AF allele frequency, IGV integrative genomics viewer.