Sequence-based mutation analysis

SNP's

Because the HFE-Gen has no annotated functional site, we can just adress the biochemical changes for each SNP. A change in functionality or stability can not described.
To compare the biochemical properties of the amino acid's, we used the very convenient function of wolfram alpha.

Mutation	Position	Database	Blosum62	PAM1	Pam250	Physicochemical changes
S/C	65	HGMD/dbSNP	-1	5	3
I/T	105	HGMD/dbSNP	-1	11	6
Q/H	127	HGMD/dbSNP	0	20	7
C/Y,S	282	HGMD/dbSNP	-2/-1	3/11	3/7
R/M	330	HGMD	-1	1	1
A/V	176	HGMD	0	13	9
R/S	6	HGMD	-1	11	6
T/I	217	dbSNP	-1	7	4
M/T	35	dbSNP	-1	6	5
R/M	58	dbSNP	-1	1	1

SIFT

Mutation	Position	Prediction	Cause disease
S/C	65	AFFECT PROTEIN FUNCTION	yes
I/T	105	AFFECT PROTEIN FUNCTION	yes
Q/H	127	TOLERATED	yes
C/Y,S	282	AFFECT PROTEIN FUNCTION	yes
R/M	330	TOLERATED	yes
A/V	176	AFFECT PROTEIN FUNCTION	yes
R/S	6	AFFECT PROTEIN FUNCTION	yes
T/I	217	TOLERATED
M/T	35	TOLERATED
R/M	58	AFFECT PROTEIN FUNCTION

The complete prediction for each position and amino acid can be found here

We got three warning messages form SIFT for which we have no explanation at this time.

WARNING: Original amino acid H at position 31 is not allowed by the prediction. 
WARNING: Original amino acid S at position 45 is not allowed by the prediction. 
WARNING: Original amino acid Y at position 230 is not allowed by the prediction.

PolyPhen-2

Mutation	Position	Prediction	Score	Cause disease
S/C	65	PROBABLY DAMAGING	0.997	yes
I/T	105			yes
Q/H	127			yes
C/Y,S	282			yes
R/M	330			yes
A/V	176			yes
R/S	6			yes
T/I	217
M/T	35
R/M	58