Table 2

DUET score for all SDHB and SDHD missense mutations described in this cohort and for rare missense variants with no or unknown pathogenicity

MutationAllele frequencymCSM stability (Kcal/mol)DUET (Kcal/mol)Predicted effect
SDHB––––
p.Lys40GluUnknown−1.741−1.774Destabilises protomer and complex
p.Arg46Gln0.000008238−0.997−1.02Destabilises protomer
p.Gly96Ser0.000008381−1.024−1.09Destabilises protomer; positive phi glycine; affect metal binding
p.Cys98ArgUnknown0.2170.316Affect metal binding; destabilse complex
p.Gly99AspUnknown−0.989−1.216Destabilises protomer and complex; affect metal binding
p.Ser100ProUnknown−0.226−0.368Affect metal binding; destabilse complex
p.Cys101TyrUnknown−1.06−1.651Destabilises protomer; affect metal binding
p.Cys113TyrUnknown−0.974−1.467Destabilises protomer and complex; affect metal binding
p.Ile127AsnUnknown−3.088−3.213Destabilises protomer. Mildly destabilises complex
p.Ile127SerUnknown−3.669−3.856Destabilises protomer
p.Val140PheUnknown−1.233−1.353Destabilises protomer. Mildly destabilises complex
p.Cys196TyrUnknown−1.407−1.77Destabilises protomer and complex; affect metal binding
p.Pro197ArgUnknown−0.954−0.784Destabilises protomer; mildly destabilises complex; affect metal binding; loss of conformational restraint
p.Trp200CysUnknown−1.442−1.205Destabilises protomer and complex
p.Arg217CysUnknown−1.916−1.948Destabilises protomer and complex
p.Arg217LeuUnknown−1.031−0.879Destabilises protomer and complex
p.Arg230GlyUnknown−1.848−2.45Destabilises protomer and complex
p.Arg230Cys0.000008252−1.739−1.836Destabilises protomer and complex
p.Arg230HisUnknown−1.903−2.133Destabilises protomer
p.Arg242CysUnknown−1.386−1.619Destabilises protomer; mildly destabilises complex; affect metal binding
p.Arg242His0.00002471−1.948−2.035Destabilises protomer; mildly destabilises complex; affect metal binding
SDHD––––
p.Pro81LeuUnknown−0.2970.036Destabilising  transmembrane
p.Asp92TyrUnknown−0.907−0.868Destabilising transmembrane
p.Tyr114CysUnknown0.2360.388Stabilising