. 2021 May 18;59(1):65–74. doi: 10.1136/jmedgenet-2020-107257

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

Family	Patient	Nucleotide change	Amino acid change	WFS1 protein location	Type of variant	Disease-associated polymorphism prediction analysis				WFS-1 protein
Family	Patient	Nucleotide change	Amino acid change	WFS1 protein location	Type of variant	SIFT	PolyPhen-2 HumVar	Mutation taster	Provean	WFS-1 protein
1	S01	c.505G>A	p.Glu169Lys	Cytosolic N-terminus	Missense	0.1 predict tolerated	0.972 probably damaging	Disease causing	−1.312 Neutral	3.8%
1	S01	c.1558C>T	p.Gln520X	Luminal loop III	Nonsense	N/A	N/A	N/A	N/A	3.8%
2	S02	c.937C>T	p.His313Tyr	Trans-membrane domain I	Missense	0.11 predict tolerated	0.628 possibly damaging	Disease causing	−0.651 Neutral	47.7%
2	S02	c.1709_14dupTGCCCC	Within minimal promotor region	Outside coding region (minimal promoter region)	Duplication	N/A	N/A	N/A	N/A	47.7%
3	S07	c.1153G>A	p.Glu385Lys	Cytosolic loop I	Missense	0.12 predicted tolerated	0.403 benign	Disease causing	−1.865 Neutral	44.6%
		Wild type	Wild type	N/A	Wild type	N/A	N/A	N/A	N/A
		Duplication of exons 4–8 in OPA1	Disease-associated OPA1 variant	N/A	Duplication	N/A	N/A	N/A	N/A
4	S03 + S04	c.911_914 dup TTGA	p.Met306X	Cytosolic N-terminus	Nonsense	N/A	N/A	N/A	N/A	0.0%
4	S03 + S04	c.1944G>A	p.Trp648X	Transmembrane domain IX	Nonsense	N/A	N/A	N/A	N/A	0.0%
5	S06	c.2319C>G	p.Tyr773X	C-terminal ER luminal domain	Nonsense	N/A	N/A	N/A	N/A	0.0%
5	S06	c.1283C>G	p.Pro428Arg	Luminal loop II	Missense	0 predict deleterious	0.995 probably damaging	Disease causing	−7.509 Deleterious	0.0%
6	S09	c.2648_2651delTCTT	p.Phe883SerfsX68	C-terminal ER luminal domain	Frameshift	N/A	N/A	N/A	N/A	0.0%
6	S09	c.906C>A	p.Tyr302X	Cytosolic N-terminus	Nonsense	N/A	N/A	N/A	N/A	0.0%
7	S10 + S11	c.1549delC	p.Arg517AlafsX5	Luminal loop III	Frameshift	N/A	N/A	N/A	N/A	0.0%
7	S10 + S11	c.1944G>A	p.Trp648X	Trans-membrane domain IX	Nonsense	N/A	N/A	N/A	N/A	0.0%

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.