Table 1

Correlation between predicted effects of missense mutations and variants and reproductive outcomes of the patients

SubstitutionPolyphen 2 scoreOur patients
Reproductive wastageLive birthNumber of unrelated patientsGeneral population
C399Y0.9991 HMYes1No
P716A0.997≥2 HMsNo1No
N913S0.994≥2 HMsExceptionally5No
G380R0.9871 HMNo1No
L398R0.968≥2 HMsNo1No
L964P0.968≥2 HMsNo1No
E340K0.9621 HMNo1No
R693W0.959≥2 HMsNo3No
D657V0.951≥2 HMsNo1No
A719V0.9421 HM or ≥3 SAsNo2No
R413W0.9151 HMYes1No
C84Y0.9091 HMNo1No
R693P0.906≥2 HMsExceptionally10No
K277Q*0.843≥2 HMsNo1No
M192L*0.701≥2 HMsNo1Yes
D722G0.677≥2 HMsNo1No
K379N0.663≥2 HMsNo2No
T1028A0.478≥2 HMs or 1 HMYes2Yes
R701C0.419≥2 HMsNo1No
F250L0.2801 HMYes1No
R693Q0.273≥2 HMsNo1No
M427T0.1891 HMYes2Yes
L750V0.110≥2 HMsNo2No
R156Q0.103≥2 HMs or ≥3SAsYes2No
K511R0.087≥3 SAsYes3Yes
R390H0.0.0411 HMYes1No
F430L0.0331 HMYes2Yes
L311I0.0251 HM or ≥3 SAsYes2Yes
Q310R0.0071 HM or ≥3 SAsYes2Yes
A481T0.007≥2 HMs or 1 HM or ≥3 SAsYes22Yes
V319I0.005≥2 HMs or 1 HM or ≥3 SAsYes47Yes
V699I0.0031 HMNA1Yes
G487E0.0021 HM or ≥3 SAsYes19Yes
R815H0.0011 HMNA1No
  • 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.