TABLE 2.

List of patients with low FH levels and/or genetic or acquired FH abnormalities.

Pat ID	Histol. group	Algor. cluster	Age of onset (y)	Rare variant	Zyg.	gnomAD global freq.	CADD	Variant classif.	SVs	C3NeF	Serum C3 (mg/dl)	Serum C4 (mg/dl)	Plasma sC5b-9 (ng/ml)	FH levels (mg/dl)	FHAAs
1073	IC	2	28	p.FH: C494Ra (SCR8)	Het	0	24.0	LPV*	Normal	Neg	70	28	1332	180	Neg
1304	IC	2	30.6	No	/	/	/	/	Heterozygous CFHR3-CFHR1 del	Pos	45	9	249	91	Neg
1773	DDD	3	11.8	No	/	/	/	/	Normal	Pos	9	24	267	91	Neg
2032	C3GN	1	24	p.FH: R78Ga,b,c,d (SCR1)	Hom	0	16	P	Normal	Neg	15	27.5	1530	133	Neg
2082	C3GN	1	0.75	p.FH: R127Ca, b (SCR2)	Het	0	33	LPV	Normal	NA	72	26	2789	151	Neg
2158	C3GN	1	41.7	p.FH: R78Ga,b,c,d (SCR1)	Hom	0	16	P	Normal	Neg	14	35	4571	154	Neg
2192	C3GN	1	9	p.FH: G133Ra (SCR2)	Het	8E-06	31	LPV§	Normal	Neg	55	20	355	178	Neg
2585	IC	2	8.8	p.FH: G879Rb (SCR15)	Het	4E-06	28	LPV	Normal	Pos	49	5	1209	119.5	Neg
2888	IC	2	16	No	/	/	/	/	Heterozygous CFH-CFHR3-CFHR1 del	Neg	8.5	23	253	156	Neg
1026	IC	2	7	No	/	/	/	/	Normal	Pos	5	6	1080	222	Pos
1837	DDD	3	10.6	No	/	/	/	/	Homozygous CFHR3-CFHR1 del	Pos	9	29	545	264	Pos
1967	IC	3	22	No	/	/	/	/	Heterozygous CFHR3-CFHR1 del	Pos	84	28.4	257	265	Pos
2047	IC	2	10	p.C3: S1063Na,b (TED domain)	Het	6.9E-05	10	VUS	Normal	Neg	70	6	235	315	Pos
2081	IC	2	8.5	No	/	/	/	/	Normal	Pos	16	13.1	1643	313	Pos
2163	IC	3	6.5	No	/	/	/	/	Normal	Pos	18	19	277	376	Pos
2557	IC	1	4.8	No	/	/	/	/	Normal	Neg	33	11	605	267	Pos
1101	DDD	3	48.7	p.FH: R1210Ca,b,e,f (SCR20)	Het	1.5E-04	12	P	Normal	Neg	154	14	368	394	Neg
1284	IC	2	0.4	p.FH: P88Ta,b (SCR2)	Hom	0	29	LPV	Normal	Neg	5.4	24.7	3596	NA*	NA
1287	IC	2	0.3	p.FH: P88Ta,b (SCR2)	Hom	0	29	LPV	Normal	Neg	47.7	45.3	2074	NA*	NA
1549	DDD	3	24.7	p.FH: R2Ia (Signal peptide)	Het	0	11	VUS	1 copy of CFHR3 + 3 copies of CFHR4	Pos	54	18	286	216	Neg

FH abnormalities are highlighted with gray color. Abbreviations and limit of normal range: Pat. ID, patient ID; Histol. Group, histologic group according to the current classification; Algor. Cluster, cluster group assigned using three-step algorithm; y, years; Zyg, zygosity; Rare variant is defined as genetic variant in coding and splicing regions of complement genes with minor allele frequency (MAF) in the gnomAD (genome aggregation database) <0.001 and with CADD (Combined Annotation Dependent Depletion) phred score ≥10. gnomAD Freq., MAF in all subjects of the gnomAD database (v2.1.1); Variant Classif., variant Classification reported in the Database on complement gene variant (https://www.complement-db.org/home.php) based on guidelines from ACMG (Richards et al., 2015) and from the KDIGO conference on aHUS and C3G (Goodship et al., 2017). When variant classification was not available in the database, the variant was classified using in silico predictions on the basis of KDIGO guidelines. P, pathogenic; LPV, likely pathogenic variant; VUS, variant of uncertain significance. SVs, structural variants defined as genomic rearrangements longer than 1 kb.

C3NeF, C3 nephritic factor;

C3, 90–180 mg/dl;

C4, 10–40 mg/dl;

Normal plasma sC5b-9 levels: ≤400 ng/ml;

Normal serum/plasma FH levels: ≥193 mg/L;

FHAAs, anti-FH antibodies.

^aIatropoulos et al. (2018).

^bOsborne et al. (2018).

^cPechtl et al. (2011).

^dCaprioli et al. (2003).

^eServais et al. (2012).

^fMaga et al. (2010).

*Pathogenic in 11 of 11 in silico tools;

^§Pathogenic in 10 of 11 in silico tools.