IFIH1 and DDX58 gene variants in pediatric rheumatic diseases

Table 1 DDX58 variants in children with immune-mediated diseases

No.	DDX58 variant	MAF	ClinVar	ACMG	IFN-I score (n.v.0-1.9 UE/L)	Diagnosis
1	c1061A>G (p.N354S)	0.0001	VUS	VUS	2.13	uSAID
2	c109G>A (p.E37K)	0.000008	Not reported	Likely non-pathogenic	N/A	uSAID
3	c.2587_2590dup (p.Cys864fs)	0.0006	Not reported	Likely pathogenic	21.0	SLE
	c.1740T>A (p.D580E)	0.11	Non-pathogenic	Non-pathogenic
4	c.431C>T (p.S144F)	0.0277	Non-pathogenic	Likely non-pathogenic	13.31	MCTD
5	c.T1740A (p.D580E)	0.11	Non-pathogenic	Non-pathogenic	8.5	SLE and MDS
6	c.1740T>A (p.D580E)	0.11	Non-pathogenic	Non-pathogenic	24.35	SLE
7	c.1740T>A (p.D580E)	0.11	Non-pathogenic	Non-pathogenic	18.93	uSAID

ACMG: The American College of Medical Genetics; GnomAD: The Genome Aggregation Database; MAF: Minor allele frequency; MCTD: Mixed connective tissue disease; MDS: Myelodysplastic syndrome; n.v.: Normal value; SLE: Systemic lupus erythematosus; uSAID: Undifferentiated systemic autoinflammatory disease; VUS: A variant of uncertain significance; N/A: Not applicable.

Table 2 IFIH1 variants in children with immune-mediated diseases

No.	IFIH1 variant	MAF	ClinVar	ACMG	IFN-score (n.v. 0-1.9 UE/L)	Diagnosis
1	c.2035_2036del (p.L679Ifs*2)	0.0001	VUS	VUS	5.4	uSAID
	c.1795delG (p.V599Ffs*5)		Not reported	Not reported
2	c.1558A>G (p.T520A)	0.0002	CIP	VUS	5.52	uSAID
3	c.1784G>A (p.R595H)	0.0001	Likely benign	VUS	29.0	JDM
4	c.1879G>T (p.E627X)	0.003	CIP	VUS	20.2	SLE-like disease
5	c.1879G>T (p.E627X)	0.003	CIP	VUS	11.3	SLE
6	c.1879G>T (p.E627X)	0.003	CIP	VUS	2.95	PFAPA
7	c.A2767G (p.I923V)	0.0126	Benign/likely benign	Benign	10.0	soJIA

ACMG: The American College of Medical Genetics; CIP: Conflicting interpretations of pathogenicity; GnomAD: The Genome Aggregation Database; JDM: Juvenile dermatomyositis; MAF: Minor allele frequency; n.v.: Normal value; PFAPA: Periodic fever with aphthous stomatitis, pharyngitis, and adenitis; SLE: Systemic lupus erythematosus; soJIA: Systemic onset juvenile idiopathic arthritis; uSAID: Undifferentiated systemic autoinflammatory disease; VUS: A variant of uncertain significance.