Task 8 (MSUD)

Results

Lab journal

Selected mutations

mutation	WT.aa	mutant.aa	physicochemical.changes	secondary.structure	BLOSUM62.score	PAM.1.250..score	PSSM..conservation.WT	PSSM..conservation.mutant	MSA..conservation.WT	MSA..conservation.mutant	SIFT	Polyphen2	MutationTaster	SNAP	DB
P38H	Pro	His	small/fixed conformation/apolar to large/aromatic/polar	-	-2	0	31	0	NA	NA	tolerated	benign	NA	NA	dbSNP
M82L	Met	Leu	sulfur-containing to aliphatic/branched	E	2	4	12	59	NA	NA	tolerated	benign	NA	NA	dbSNP
T151M	Thr	Met	small/polar to apolar/sulfur-containing	-	-1	-1	8	0	NA	NA	tolerated	probably/possibly damaging	NA	NA	HGMD
A222T	Ala	Thr	apolar to polar	H	0	1	64	4	NA	NA	affect protein function	probably damaging	NA	NA	dbSNP
C264W	Cys	Trp	small/sulfur-containing to large/aromatic	E	-2	-8	52	0	NA	NA	affect protein function	probably/possibly damaging	NA	NA	HGMD
R265W	Arg	Trp	positively-charged to aromatic/larger	E	-3	2	12	0	NA	NA	affect protein function	probably damaging	NA	NA	HGMD
R314Q	Arg	Gln	guanidin/large/positively-charged to amin	H	1	1	23	0	NA	NA	affect protein function	probably damaging	NA	NA	dbSNP
R346H	Arg	His	hydrophilic to hydrophobic/aromatic	-	0	2	92	0	NA	NA	affect protein function	probably damaging	NA	NA	HGMD
I361V	Ile	Val	smaller	H	3	4	64	10	NA	NA	tolerated	benign/possibly damaging	NA	NA	dbSNP
Y413H	Tyr	His	uncharged to positively-charged	-	2	0	74	1	NA	NA	affect protein function	probably damaging	NA	NA	HGMD

SIFT

The following table shows the prediction of mutation effects by SIFT. 6 out of 10 mutations are predicted to affect protein function.

mutation	prediction	score	median sequence conservation	sequences represented at position
P38H	tolerated	0.16	3.16	17
M82L	tolerated	0.56	3.03	43
T151M	tolerated	0.05	3.03	46
A222T	affect protein function	0.04	3.03	46
C264W	affect protein function	0.00	3.03	46
R265W	affect protein function	0.00	3.03	46
R314Q	affect protein function	0.01	3.03	46
R346H	affect protein function	0.00	3.03	46
I361V	tolerated	0.12	3.03	46
Y413H	affect protein function	0.00	3.03	46

Polyphen2

The prediction resuls of Polyphen2 are shown in the following table. 7 out of 10 mutations are predicted to be probably damaging (at least for the trained set HumDiv). For the mutation T151M, this does not agree with the results of SIFT. But for this mutations the Polyphen scores are also the lowest of all mutations that are predicted to be damaging. So Polyphen sees an uncertainty for this mutation too, if it is damaging.

	HumDiv				HumVar
mutation	prediction	score	sensitivity	specificity	prediction	score	sensitivity	specificity
P38H	benign	0.118	0.93	0.96	benign	0.042	0.93	0.62
M82L	benign	0.002	0.99	0.30	benign	0.006	0.97	0.45
T151M	probably damaging	0.963	0.78	0.95	possibly damaging	0.622	0.80	0.85
A222T	probably damaging	1.000	0.00	1.00	probably damaging	0.943	0.65	0.91
C264W	probably damaging	0.989	0.72	0.97	possibly damaging	0.887	0.71	0.89
R265W	probably damaging	1.000	0.00	1.00	probably damaging	1.000	0.00	1.00
R314Q	probably damaging	1.000	0.00	1.00	probably damaging	0.998	0.18	0.98
R346H	probably damaging	1.000	0.00	1.00	probably damaging	0.993	0.47	0.96
I361V	benign	0.386	0.90	0.89	possibly damaging	0.610	0.80	0.83
Y413H	probably damaging	1.000	0.00	1.0	probably damaging	0.999	0.09	0.99