Table 1.

The sequence-based classification of nonsynonymous mutations of SPIKE protein (S-protein) as increasing or decreasing in stability by applying iStable Server.

Domain	Mutation	I-Mutant2.0 SEQ		Mupro		Meta Result (iStable)
		DDG	Prediction	Score	Prediction	Score	Prediction
SP	L5F	−0.63	Decrease	−0.72	Decrease	0.71	Decrease
	L8V	−2.82	Decrease	−0.45	Decrease	0.83	Decrease
	L8W	−1.20	Decrease	−0.62	Decrease	0.82	Decrease
NTD	L18F	−0.82	Decrease	−1.00	Decrease	0.86	Decrease
	H49Y	0.69	Increase	0.98	Increase	0.84	Increase
	S50L	−0.04	Decrease	1	Increase	0.52	Increase
	L54F	−0.88	Decrease	−1	Decrease	0.82	Decrease
	S71F	0.41	Increase	0.02	Increase	0.82	Increase
	T76I	−0.93	Decrease	−1	Decrease	0.60	Decrease
	V120I	−0.57	Decrease	−0.69	Decrease	0.78	Decrease
	D138Y	0.08	Decrease	−0.67	Decrease	0.57	Decrease
	Y145H	−1.43	Decrease	−1	Decrease	0.82	Decrease
	M153T	−1.07	Decrease	−0.67	Decrease	0.84	Decrease
	F157S	−1.94	Decrease	−1	Decrease	0.89	Decrease
	L176F	−0.88	Decrease	−1	Decrease	0.81	Decrease
	G181V	−0.48	Decrease	−0.15	Decrease	0.81	Decrease
	D215H	−0.97	Decrease	−1	Decrease	0.69	Decrease
	S221L	−0.25	Decrease	1	Increase	0.51	Increase
	S221W	0.14	Increase	0.89	Increase	0.77	Increase
	Q239K	−0.56	Increase	−0.01	Decrease	0.51	Increase
	S247R	0.01	Increase	0.50	Increase	0.78	Increase
	S254F	0.21	Increase	0.44	Increase	0.82	Increase
	W258L	−0.84	Decrease	0.11	Increase	0.62	Increase
	A262T	−0.73	Decrease	−0.83	Decrease	0.77	Decrease
CTD/RBD	V367F	−2.07	Decrease	−0.19	Decrease	0.79	Decrease
	S438F	0.00	Increase	0.75	Increase	0.82	Increase
	G476S	−1.45	Decrease	−0.45	Decrease	0.82	Decrease
	V483A	−1.46	Decrease	−0.51	Decrease	0.75	Decrease
	N501Y	0.18	Increase	0.39	Increase	0.51	Increase
Linker (S1/S2)	L611F	−0.72	Decrease	−1	Decrease	0.82	Decrease
	D614G	−1.10	Decrease	0.19	Increase	0.68	Increase
	Q675H	−0.64	Decrease	−0.06	Decrease	0.80	Decrease
	Q675R	−0.06	Decrease	0.50	Increase	0.59	Increase
	A706V	−0.26	Decrease	0.16	Increase	0.52	Decrease
FP	T791I	−0.35	Decrease	−1	Decrease	0.66	Decrease
S2	P809S	−1.59	Decrease	−1	Decrease	0.79	Decrease
	A831V	−0.06	Decrease	0.85	Increase	0.56	Increase
	D839Y	0.04	Increase	0.31	Increase	0.80	Increase
	A845S	−0.77	Decrease	−1	Decrease	0.88	Decrease
	A845V	−0.20	Decrease	0.09	Increase	0.51	Increase
	A846V	−0.18	Decrease	0.89	Increase	0.54	Decrease
	A852V	−0.14	Decrease	0.72	Increase	0.58	Increase
	A879S	−0.62	Decrease	−0.50	Decrease	0.86	Decrease
	V1040F	−1.72	Decrease	−0.92	Decrease	0.83	Decrease
	P1143L	−0.64	Decrease	0.16	Increase	0.55	Increase
	P1162L	−0.94	Decrease	−0.39	Decrease	0.81	Decrease
HR1	D936H	−0.94	Decrease	−0.61	Decrease	0.76	Decrease
	D936Y	−0.58	Decrease	0.09	Increase	0.69	Increase
	S939F	−0.09	Increase	−0.24	Decrease	0.52	Decrease
	S940F	0.09	Increase	0.99	Increase	0.75	Increase
	S940T	−0.07	Increase	0.55	Increase	0.81	Increase
	T941A	−1.04	Decrease	−0.51	Decrease	0.72	Decrease
	S943P	−0.21	Increase	0.47	Increase	0.81	Increase
HR2	D1163G	−1.78	Decrease	−0.83	Decrease	0.75	Decrease
TM	I1216T	−1.96	Decrease	−1	Decrease	0.86	Decrease
	M1229I	−0.85	Decrease	−1	Decrease	0.71	Decrease
	M1237L	−0.91	Decrease	−0.25	Decrease	0.82	Decrease
	M1237I	−0.75	Decrease	−0.63	Decrease	0.74	Decrease
CT	C1247F	0.01	Decrease	−0.42	Decrease	0.69	Decrease
	C1254F	−0.13	Decrease	−0.87	Decrease	0.76	Decrease
	D1260 N	−0.94	Decrease	−0.57	Decrease	0.85	Decrease
	P1263L	−0.66	Decrease	−0.41	Decrease	0.80	Decrease