Table 2

WFS1 variants seen in patients with WFS reported in this study, in silico analysis for polymorphism prediction and experimentally measured WFS1 protein level

FamilyPatientNucleotide changeAmino acid changeWFS1 protein locationType of variantDisease-associated polymorphism prediction analysisWFS-1 protein
SIFTPolyPhen-2 HumVarMutation tasterProvean
1S01c.505G>Ap.Glu169LysCytosolic N-terminusMissense0.1 predict tolerated0.972
probably damaging
Disease causing−1.312
Neutral
3.8%
c.1558C>Tp.Gln520XLuminal loop IIINonsenseN/AN/AN/AN/A
2S02c.937C>Tp.His313TyrTrans-membrane domain IMissense0.11 predict tolerated0.628
possibly damaging
Disease causing−0.651
Neutral
47.7%
c.1709_14dupTGCCCCWithin minimal promotor regionOutside coding region (minimal promoter region)DuplicationN/AN/AN/AN/A
3S07c.1153G>Ap.Glu385LysCytosolic loop IMissense0.12 predicted tolerated0.403
benign
Disease causing−1.865
Neutral
44.6%
Wild typeWild typeN/AWild typeN/AN/AN/AN/A
Duplication of exons 4–8 in OPA1Disease-associated OPA1 variantN/ADuplicationN/AN/AN/AN/A
4S03
+
S04
c.911_914 dup TTGAp.Met306XCytosolic N-terminusNonsenseN/AN/AN/AN/A0.0%
c.1944G>Ap.Trp648XTransmembrane domain IXNonsenseN/AN/AN/AN/A0.0%
5S06c.2319C>Gp.Tyr773XC-terminal ER luminal domainNonsenseN/AN/AN/AN/A0.0%
c.1283C>Gp.Pro428ArgLuminal loop IIMissense0 predict deleterious0.995
probably damaging
Disease causing−7.509
Deleterious
6S09c.2648_2651delTCTTp.Phe883SerfsX68C-terminal ER luminal domainFrameshiftN/AN/AN/AN/A0.0%
c.906C>Ap.Tyr302XCytosolic N-terminusNonsenseN/AN/AN/AN/A
7S10
+
S11
c.1549delCp.Arg517AlafsX5Luminal loop IIIFrameshiftN/AN/AN/AN/A0.0%
c.1944G>Ap.Trp648XTrans-membrane domain IXNonsenseN/AN/AN/AN/A0.0%
  • SIFT (0.0–0.05 considered deleterious; 0.05–1.0 predicted tolerated (benign)). Polyphen-2 (0.0–0.15 predicted benign; 0.15–1.0 possibly damaging; 0.85–1.0 more confidently predicted damaging). Provean (≤−2.5 ‘deleterious’; ≥−2.5 ‘neutral’. Polymorphism prediction software consulted in March 2019. Polymorphism prediction software consulted in March 2019.