Table 1. Homozygous or potentially compound-heterozygous rare nonsynonymous variants of the OAS and RNASEL genes in MIS-C patients.
Homozygous or potentially compound-heterozygous nonsynonymous variants with a minor allele frequency (MAF) < 0.01 (gnomAD) found in our cohort of MIS-C patients. CADD_Phred, combined annotation-dependent depletion Phred score; Exp function, experimental function of each variant as tested in the RNase L–dependent rRNA degradation assay (OAS1, OAS2, RNase L) and FRET assay (OAS1, OAS2); Hom, homozygous; Het, heterozygous.
| Gene | Nucleotide change | Amino acid change | Zygosity | MAF (gnomAD) | CADD_Phred | Exp function |
| OAS1 | c.139C>T | p.Arg47* (R47*) | Hom | 0.00017327 | 36 | LOF |
| OAS2 | c.1604G>A | p.Arg535Gln (R535Q) | Hom | 0.00028695 | 13.58 | Hypomorph |
| OAS2 | c.773A>T | p.Gln258Leu (Q258L) | Het | – | 3.888 | Hypomorph |
| OAS2 | c.868G>A | p.Val290Ile (V290I) | Het | 0.0005153 | 5.585 | Hypomorph |
| OAS3 | c.145G>A | p.Ala49Thr (A49T) | Het | 0.00243639 | 9.48 | Isomorph |
| OAS3 | c.1475G>A | p.Arg492His (R492H) | Het | 0.0054987 | 9.95 | Isomorph |
| OAS3 | c.1703G>A | p.Arg568Lys (R568K) | Het | 0.00104951 | 0.472 | Isomorph |
| OAS3 | c.2795G>A | p.Arg932Gln (R932Q) | Het | 0.0094 | 23.2 | LOF |
| OAS3 | c.3089A>G | p.Gln1030Arg (Q1030R) | Het | – | 23.9 | Isomorph |
| OAS3 | c.1586A>G | p.Gln529Arg (Q529R) | Het | 0.00000401 | 5.85 | Isomorph |
| OAS3 | c.792C>A | p.His264Gln (H264Q) | Het | 0.001001261 | 0.924 | Isomorph |
| OAS3 | c.442C>T | p.Pro148Ser (P148S) | Het | 0.000036 | 22.9 | Isomorph |
| OAS3 | c.3259G>A | p.Val1087Met (V1087M) | Het | 0.003936537 | 22.5 | Isomorph |
| RNASEL | c.790A>G | p.Ile264Val (I264V) | Hom | 0.00000401 | 6.597 | Isomorph |
| RNASEL | c.793G>T | p.Glu265* (E265*)† | Hom | 0.0031 | 33 | LOF |
| RNASEL | c.175G>A | p.Gly59Ser (G59S)† | Hom | 0.0031 | 22.9 | Isomorph |
†RNASEL variants p.E265* and p.G59S were in complete linkage disequilibrium (https://www.internationalgenome.org), forming a haplotype.