Table 2.
Functional analysis in previously characterized FH variants (n = 26)
| Transcript | Protein | Expression | GP hemolysis HR50 (0.71-1.29)* |
C3b binding BD50 (0.33-1.67)* |
DAA (<12.5)* |
FI cofactor activity (<2.5)* | Classification (this study) |
Classification (previously reported) |
Reference |
|---|---|---|---|---|---|---|---|---|---|
| c.157C>T | R53C | N | 2.46 | 1.14 | 32.9 | 1.7 | Pathogenic | Pathogenic | 31 |
| c.184G>A | V62I | N | 0.91 | 1.04 | 4.2 | 1.2 | Benign | Polymorphism | 32 |
| c.232A>G | R78G | N | 3.36 | 1.68 | 36.6 | 19.7 | Pathogenic | Pathogenic | 33 |
| c.524G>C | R175P | N | > 8 | 2.49 | 46.6 | 72.6 | Pathogenic | Pathogenic | 34 |
| c.653G>A | G218E | N | 7.33 | 8.10 | 43.6 | 47.5 | Pathogenic | Nonexpressed | 35 |
| c.1189G>A | G397R | W | 1.12 | — | 20.5 | 2.3 | Pathogenic | Nonexpressed | 36 |
| c.1198C>A | Q400K† | N | 0.94 | 1.18 | 8.1 | 1.9 | Benign | Nonexpressed | 22 |
| c.1204C>A | H402Y | N | 1.22 | 1.00 | 5.6 | 1.7 | Benign | Polymorphism | — |
| c.1231T>A | S411T | N | 1.00 | 0.98 | 7.9 | 1.8 | Benign | Benign | 5 |
| c.1292G>A | C431Y | W | 1.12 | 1.54 | 12.9 | 2.6 | Pathogenic | Nonexpressed | 36 |
| c.1343G>A | C448Y | W | 1.09 | 1.32 | 6.8 | 1.8 | Pathogenic | Nonexpressed | 37 |
| c.1424A>C | Y475S† | N | 0.93 | 1.02 | 6.4 | 1.7 | Benign | Nonexpressed | 38 |
| c.2695T>G | Y899D | W | 0.70 | 0.83 | 4.1 | 1.5 | Pathogenic | Nonexpressed | 39 |
| c.2850G>T | Q950H | N | 1.14 | 1.52 | 9.7 | 1.6 | Benign | Polymorphism | 40 |
| c.2867C>T | T956M | N | 1.19 | 0.81 | 7.7 | 1.9 | Benign | Polymorphism | 31 |
| c.2918G>A | C973Y | W | 1.11 | 0.80 | 6.5 | 1.9 | Pathogenic | Nonexpressed | 41 |
| c.3148A>T | N1050Y | N | 1.07 | 1.77 | 7.8 | 1.6 | Benign | Polymorphism | 42 |
| c.3231T>G | C1077W | W | 1.20 | 1.11 | 11.1 | 3.9 | Pathogenic | Nonexpressed | 43 |
| c.3355G>A | D1119N | N | 3.07 | 1.09 | 42.3 | 53.6 | Pathogenic | Pathogenic | 31 |
| c.3356A>G | D1119G | N | 2.71 | 0.78 | 37.1 | 27.8 | Pathogenic | Pathogenic | 44 |
| c.3425A>G | Y1142C | N | 5.03 | 8.78 | 60.3 | 73.7 | Pathogenic | Pathogenic | 45 |
| c.3454T>A | C1152S | F | — | — | — | — | Pathogenic | Nonexpressed | 46 |
| c.3497C>T | P1166L | N | 2.71 | 6.93 | 48.3 | 32.9 | Pathogenic | Pathogenic | 31 |
| c.3572C>T | S1191L | N | 1.13 | 1.08 | 25.6 | 18.8 | Pathogenic | Pathogenic | 47 |
| c.3628C>T | R1210C | N | 1.51 | 1.20 | 8.8 | 2.1 | Pathogenic | Pathogenic | 8 |
| c.3644G>A | R1215Q | N | 4.75 | 1.79 | 38.1 | 18.3 | Pathogenic | Pathogenic | 16,48 |
Abnormal values are shown in bold type.
F, failed to express in vitro; GP, guinea pig; N, normal; W, weak (decreased) intensity of band corresponding to FH in nonreducing SDS-PAGE; –, not performed or not saturable binding (see “Individual variant datasheets” for details).
Normal ranges are in parenthesis. HR50 refers to the concentration fold of FH mutant needed to confer 50% protection from lysis compared with the wild-type FH protein in the guinea pig hemolysis assay; BD50 refers to the concentration fold of FH mutant needed to confer similar binding to C3b compared with the wild-type FH protein (see “Methods” for details).
FH variants that associate with quantitative deficiencies in patients but express normally in vitro and are functionally undistinguishable from the wild-type FH in vitro.