Correlation between predicted effects of missense mutations and variants and reproductive outcomes of the patients
| Substitution | Polyphen 2 score | Our patients | |||
| Reproductive wastage | Live birth | Number of unrelated patients | General population | ||
| C399Y | 0.999 | 1 HM | Yes† | 1 | No |
| P716A | 0.997 | ≥2 HMs | No | 1 | No |
| N913S | 0.994 | ≥2 HMs | Exceptionally‡ | 5 | No |
| G380R | 0.987 | 1 HM | No | 1 | No |
| L398R | 0.968 | ≥2 HMs | No | 1 | No |
| L964P | 0.968 | ≥2 HMs | No | 1 | No |
| E340K | 0.962 | 1 HM | No | 1 | No |
| R693W | 0.959 | ≥2 HMs | No | 3 | No |
| D657V | 0.951 | ≥2 HMs | No | 1 | No |
| A719V | 0.942 | 1 HM or ≥3 SAs | No | 2 | No |
| R413W | 0.915 | 1 HM | Yes | 1 | No |
| C84Y | 0.909 | 1 HM | No | 1 | No |
| R693P | 0.906 | ≥2 HMs | Exceptionally‡ | 10 | No |
| K277Q* | 0.843 | ≥2 HMs | No | 1 | No |
| M192L* | 0.701 | ≥2 HMs | No | 1 | Yes |
| D722G | 0.677 | ≥2 HMs | No | 1 | No |
| K379N | 0.663 | ≥2 HMs | No | 2 | No |
| T1028A | 0.478 | ≥2 HMs or 1 HM | Yes | 2 | Yes |
| R701C | 0.419 | ≥2 HMs | No | 1 | No |
| F250L | 0.280 | 1 HM | Yes | 1 | No |
| R693Q | 0.273 | ≥2 HMs | No | 1 | No |
| M427T | 0.189 | 1 HM | Yes | 2 | Yes |
| L750V | 0.110 | ≥2 HMs | No | 2 | No |
| R156Q | 0.103 | ≥2 HMs or ≥3SAs | Yes | 2 | No |
| K511R | 0.087 | ≥3 SAs | Yes | 3 | Yes |
| R390H | 0.0.041 | 1 HM | Yes | 1 | No |
| F430L | 0.033 | 1 HM | Yes | 2 | Yes |
| L311I | 0.025 | 1 HM or ≥3 SAs | Yes | 2 | Yes |
| Q310R | 0.007 | 1 HM or ≥3 SAs | Yes | 2 | Yes |
| A481T | 0.007 | ≥2 HMs or 1 HM or ≥3 SAs | Yes | 22 | Yes |
| V319I | 0.005 | ≥2 HMs or 1 HM or ≥3 SAs | Yes | 47 | Yes |
| V699I | 0.003 | 1 HM | NA | 1 | Yes |
| G487E | 0.002 | 1 HM or ≥3 SAs | Yes | 19 | Yes |
| R815H | 0.001 | 1 HM | NA | 1 | No |
Polyphen 2 scores vary between 1 (for the most severe substitution) and 0 (for the most benign) and are listed by decreasing severity from top to bottom. NA indicates no available data on the other reproductive outcomes of the patient. Different outcomes in different patients are indicated by ‘or’.
↵* Missense variants found in patients on haplotypes carrying other mutations.
↵† Presence of several congenital malformations in the live birth which are described in the Materials and Methods section.
↵‡ A single live birth in one patient who is compound heterozygous for N913S and R693P among six patients with N913S (who had had a total of 24 pregnancies) and 10 patients with R693P (who had had a total of 36 pregnancies).
HM, hydatidiform mole; SA, spontaneous abortion.