Difference between revisions of "Sequence-based mutation analysis HEXA"

From Bioinformatikpedia
(→‎rs1800430: Asn -> Asp)
(→‎Analysis of the mutations)
Line 63: Line 63:
 
We created for each mutation an extra page. The summary of the analysis can be seen in the Summary Section.
  
We created for each mutation an extra page. The summary of the analysis can be seen in the Summary Section.
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs4777505 rs4777505: Asn -> Ser]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs4777505 rs4777505: Asn -> Ser]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907979 rs121907979: Leu -> Arg]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907979 rs121907979: Leu -> Arg]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs61731240 rs61731240: His -> Asp]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs61731240 rs61731240: His -> Asp]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907974 rs121907974: Phe -> Ser]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907974 rs121907974: Phe -> Ser]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs61747114 rs61747114: Leu -> Phe]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs61747114 rs61747114: Leu -> Phe]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs1054374 rs1054374: Ser -> Ile]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs1054374 rs1054374: Ser -> Ile]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907967 rs121907967: Trp -> TER]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907967 rs121907967: Trp -> TER]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs1800430 rs1800430: Asn -> Asp]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs1800430 rs1800430: Asn -> Asp]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907982 rs121907982: Ile -> Val]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907982 rs121907982: Ile -> Val]]
   
−
[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907968 rs121907968: Trp -> Arg]]
 +
*[[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907968 rs121907968: Trp -> Arg]]
   
−  
−
===rs4777505: Asn -> Ser ===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Asn
  
−
|Ser
  
−
|consequences
  
−
|-
  
−
|polar, small, hydrophilic, negatively charged
  
−
|polar, tiny, hydrophilic, neutral
  
−
|Both amino acids are polar and hydrophilic. Ser is tiny, Asn therefore is a small amino acid. The biggest difference between these two amino acid is, that Asn is negatively charged and Ser is neutral. But this is not that big difference and therefore we suggest, that this mutation do not delete the structure and function of the protein.
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:N29_2.png|thumb|150px|Amino acid Asparagine]]
  
−
|[[Image:29S_2.png|thumb|150px|Amino acid Serine]]
  
−
|[[Image:N29S.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|20
  
−
|36 (Asp)
  
−
|0 (Cys, Met)
  
−
|5
  
−
|7 (Asp)
  
−
|2 (Cys, Leu, Phe, Trp)
  
−
|1
  
−
|1 (Asp, His, Ser)
  
−
| -4 (Trp)
  
−
|-
  
−
|}
  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_1.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
CCHHHHHHHHHHHHHCCCCCCCEEEEEEE<font color="red">E</font>EECCCEEEEECCCEEEEECCCCCCC...
  
−
PsiPred:
  
−
CHHHHHHHHHHHHHHHCCCCCCCCCCCCE<font color="red">E</font>EECCCEEEEECCCEEEEECCCCCCC...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:29_mut.png|thumb|250px|Mutation at position 29]]
  
−
| [[Image:29_mut_detail.png|thumb|250px|Mutation at position 29 - detailed view]]
  
−
|}
  
−  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|S
  
−
|Neutral
  
−
|8
  
−
|96%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs4777505_SNAP here]]
  
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:29_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><tr><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=black>w</font></td><th>29N</th><td>0.78</td><td><font color=green>c</font></td><td><font color=black>f</font></td><td><font color=black>M</font></td><td><font color=red>H</font></td><td><font color=black>i</font></td><td><font color=green>Y</font></td><td><font color=black>p</font></td><td><font color=black>V</font></td><td><font color=black>g</font></td><td><font color=black>L</font></td><td><font color=red>R</font></td><td><font color=green>N</font></td><td><font color=blue>d</font></td><td><font color=green>Q</font></td><td><font color=green>T</font></td><td><font color=black>A</font></td><td><font color=green>S</font></td><td><font color=red>K</font></td><td><font color=blue>E</font></td><td><font color=gray> </font></td></tr></table>
  
−
|}
  
−
<br><br>
  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_1_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_1_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs121907979: Leu -> Arg===
  
−  
−
'''Pysicochemical Properities'''
  
−  
−
First of all, we explored the amino acid properties and compared them for the original and the mutated amino acid. Therefore we created the possible effect that the mutation could have on the protein.
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Leu
  
−
|Arg
  
−
|consequences
  
−
|-
  
−
|aliphatic, hydrophobic, neutral
  
−
|positive charged, polar, hydrophilic
  
−
|Leucine is smaller and without a positive charge. Therefore, Arg is too big for the position of Leu, therefore, the change of Leu with Arg has to cause changes in the 3D structure of the protein. Furthermore, Leu is a hydrophobic amino acid, whereas Arg is hydrophilic. This is the complete contrary and therefore we suggest, that the protein will not function any longer.
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
In the next step, we created the visualization of the muation with PyMol. Therefore we created a picture for the original amino acid, for the new mutated amino acid and finally for both together in one picture whereas the mutation is white colored.
 
−
The following pictures display that the mutated amino acid Arginine has a longer chain than Leucine. Contrary Leucine comes to a fork at the end of its rest. This shows that the amino acids have some structural differences that are not drastical, but can be essential.
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:L39.png|thumb|150px|Amino acid Leucine]]
  
−
|[[Image:39R.png|thumb|150px|Amino acid Arginine]]
  
−
|[[Image:L39R.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−  
−
Afterwards, we looked at the values of the substitution matrices PAM1, PAM250 and BLOSSUM62.
 
−
Therefore we looked detailed at the three values: the value for accoding amino acid substitution, the most frequent value for the substitution of the examined amino acid and the rarest substitution.
  
−  
−
In this case, the substitution of Leucine to Arginine has very low values that are near the values for the rarest subsitution for PAM1 and PAM250. Furthermore, the value for the most frequent substitution differs also a lot from the value for this certain mutation for both PAMs. Contrary for BLOSUM62 the value for the amino acid subsitution Leucine to Arginine is average. This means the most frequent subsitution value is as far as the rarerest subsitution from the the underlying value.
 
−
The difference between the two PAMs and BLOSUM62 can be ascribed to the different preparations of these two kind of substitutions matrices. The PAM-matrices is an evolutionary model whereas BLOSUM is based on protein famalies. Therefore probably this mutation is evolutionary not that unlikely whereas within a protein family it is unusual.
 
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|1
  
−
|22 (Ile)
  
−
|0 (Asp, Cys)
  
−
|4
  
−
|20 (Met)
  
−
|2 (Cys)
  
−
| -2
  
−
|0 (Phe)
  
−
| -4 (Asp, Gly)
  
−
|-
  
−
|}
  
−  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_2.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
CCHHHHHHHHHHHHHCCCCCCCEEEEEEEEEECCCEEEE<font color="red">E</font>CCCEEEEECCCCCCC...
  
−
PsiPred:
  
−
CHHHHHHHHHHHHHHHCCCCCCCCCCCCEEEECCCEEEE<font color="red>E</font>CCCEEEEECCCCCCCC...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:39_mut.png|thumb|250px|Mutation at position 39]]
  
−
| [[Image:39_mut_detail.png|thumb|250px|Mutation at position 39 - detailed view]]
  
−
|}
  
−  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|R
  
−
|Non-neutral
  
−
|5
  
−
|87%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907979_SNAP here]]
  
−  
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:39_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=red>h</font></td><td><font color=blue>d</font></td><td><font color=black>w</font></td><td><font color=green>q</font></td><td><font color=black>p</font></td><td><font color=green>n</font></td><td><font color=blue>e</font></td><td><font color=green>c</font></td><td><font color=red>r</font></td><td><font color=black>g</font></td><td><font color=green>s</font></td><td><font color=red>k</font></td><td><font color=green>y</font></td><td><font color=green>t</font></td><td><font color=black>a</font></td><td><font color=black>f</font></td><td><font color=black>m</font></td><th>39L</th><td>0.79</td><td><font color=black>V</font></td><td><font color=black>I</font></td><td><font color=black>L</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr></table>
 
−
|}
  
−
<br><br>
  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_2_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_2_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs61731240: His -> Asp===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|His
  
−
|Asp
  
−
|consequences
  
−
|-
  
−
|aromatic, positive charged, polar, hydrophilic
  
−
|negative charged, small, polar, hydrophilic
 
−
|On the one side, both amino acids are polar, but on the other side, His is positively charged, while Asp is negatively charged, which is an essential difference between these both amino acids. Therefore it is very likely, that this change causes big changes in the structure of the protein and the protein therefore will probably not work any longer. Furthermore, the structure of the two amino acids is very different, because of the aromatic ring of the His.
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:H179.png|thumb|150px|Amino acid Histidine]]
  
−
|[[Image:179D.png|thumb|150px|Amino acid Aspartate]]
  
−
|[[Image:H179D.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|3
  
−
|20 (Gln)
  
−
|0 (Ile, Met)
  
−
|4
  
−
|7 (Gln)
  
−
|2 (Ala, Cys, Gly, Ile, Leu, Met, Phe, Thr, Trp, Val)
  
−
| -1
  
−
|2 (Tyr)
  
−
| -3 (Cys, Ile, Leu, Val)
  
−
|-
  
−
|}
  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_3.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...EEEECCCCCEEEEEECCCC<font color="red">C</font>CCHHHHHHHHHHHHHHCCCEEEEEEECCCCCCCCC...
  
−
PsiPred:
  
−
...EEECCCCCCCCCCCCCCCC<font color="red">C</font>CCHHHHHHHHHHHHHCCCCEEEEEECCCCCCCEEC...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:179_mut.png|thumb|250px|Mutation at position 179]]
  
−
| [[Image:179_mut_detail.png|thumb|250px|Mutation at position 179 - detailed view]]
  
−
|}
  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|D
  
−
|Non-neutral
  
−
|6
  
−
|93%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs61731240_SNAP here]]
 
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:179_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=black>m</font></td><td><font color=black>w</font></td><td><font color=black>f</font></td><td><font color=green>c</font></td><td><font color=black>i</font></td><td><font color=green>y</font></td><td><font color=black>v</font></td><td><font color=black>l</font></td><td><font color=green>t</font></td><td><font color=black>a</font></td><td><font color=green>s</font></td><td><font color=black>p</font></td><td><font color=blue>e</font></td><td><font color=red>r</font></td><td><font color=green>n</font></td><td><font color=blue>d</font></td><td><font color=red>k</font></td><td><font color=black>g</font></td><td><font color=green>Q</font></td><th>179H</th><td>0.99</td><td><font color=red>H</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr></table>
 
−
|}
  
−
<br><br>
  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_3_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_3_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs121907974: Phe -> Ser ===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Phe
  
−
|Ser
  
−
|consequences
  
−
|-
  
−
|polar, tiny, hydrophilic, neutral
  
−
|aliphatic, hydrophobic, neutral
  
−
|Ile is much bigger than Ser and also is branched, because it is an aliphatic amino acid. Therefore the structure of both amino acids is really different and Ile is to big for the position where Ser was. Therefore, there has to be a big change in the 3D structure of the protein and the protein probably will loose its function.
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:F211.png|thumb|150px|Amino acid Phenylalanine]]
  
−
|[[Image:211S.png|thumb|150px|Amino acid Serine]]
  
−
|[[Image:F211S.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|2
  
−
|28 (Tyr)
  
−
|0 (Asp, Cys, Glu, Lys, Pro, Val)
  
−
|2
  
−
|20 (Tyr)
  
−
|1 (Arg, Asp, Cys, Gln, Glu, Gly, Lys, Pro)
  
−
| -2
  
−
|3 (Tyr)
  
−
| -4 (Pro)
  
−
|-
  
−
|}
  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_4.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...EEEECCCCCEEEEEECCCCCCCHHHHHHHHHHHHHHCCCEEEEEEECCCCC<font color="red">C</font>CCC...
  
−
PsiPred:
  
−
...EEECCCCCCCCCCCCCCCCCCCHHHHHHHHHHHHHCCCCEEEEEECCCCCC<font color="red">C</font>EEC...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:211_mut.png|thumb|250px|Mutation at position 211]]
  
−
| [[Image:211_mut_detail.png|thumb|250px|Mutation at position 211 - detailed view]]
  
−
|}
  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|S
  
−
|Non-neutral
  
−
|5
  
−
|87%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907974_SNAP here]]
 
−  
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:211_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=green>y</font></td><td><font color=black>w</font></td><td><font color=black>v</font></td><td><font color=green>t</font></td><td><font color=green>s</font></td><td><font color=red>r</font></td><td><font color=green>q</font></td><td><font color=black>p</font></td><td><font color=green>n</font></td><td><font color=black>m</font></td><td><font color=black>l</font></td><td><font color=red>k</font></td><td><font color=black>i</font></td><td><font color=red>h</font></td><td><font color=black>g</font></td><td><font color=blue>e</font></td><td><font color=blue>d</font></td><td><font color=green>c</font></td><td><font color=black>a</font></td><th>211F</th><td>1.00</td><td><font color=black>F</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr></table>
 
−
|}
  
−
<br><br>
  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_4_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_4_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs61747114: Leu -> Phe===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Leu
  
−
|Phe
  
−
|consequences
  
−
|-
  
−
|aliphatic, hydrophobic, neutral
  
−
|aromatic, hydrophobic, neutral
 
−
|Leu is an aliphatic amino acid, wheras Phe is an aromatic amino acid. This means, that Phe has an aromatic ring in its structure. But both amino acids are relatively big and so it is possible, that the exchange of this amino acids do not change the structure of the protein that much. Therefore, we suggest it is possible, that the protein will work.
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:L248.png|thumb|150px|Amino acid Leucine]]
  
−
|[[Image:248W.png|thumb|150px|Amino acid Phenylalanine]]
  
−
|[[Image:L248W.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|13
  
−
|45 (Met)
  
−
|0 (Asp, Cys)
  
−
|13
  
−
|20 (Met)
  
−
|2 (Cys)
  
−
|0
  
−
|2 (Ile, Met)
  
−
| -4 (Asp, Gly)
  
−
|-
  
−
|}
  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_5.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...HHHHHHHH<font color="red">C</font>CCEEEECCCCCHHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCCCCC...
  
−
PsiPred:
  
−
...HHHHHHHH<font color="red">C</font>CCEEEECCCCCHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCCCCCH...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:248_mut.png|thumb|250px|Mutation at position 248]]
  
−
| [[Image:248_mut_detail.png|thumb|250px|Mutation at position 248 - detailed view]]
  
−
|}
  
−  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|F
  
−
|Neutral
  
−
|3
  
−
|78%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs61747114_SNAP here]]
 
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:248_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=green>c</font></td><td><font color=black>w</font></td><td><font color=black>p</font></td><td><font color=blue>e</font></td><td><font color=green>n</font></td><td><font color=red>k</font></td><td><font color=black>g</font></td><td><font color=red>r</font></td><td><font color=green>s</font></td><td><font color=green>t</font></td><td><font color=red>h</font></td><td><font color=black>a</font></td><td><font color=green>Q</font></td><th>248L</th><td>1.00</td><td><font color=green>Y</font></td><td><font color=black>I</font></td><td><font color=blue>D</font></td><td><font color=black>V</font></td><td><font color=black>F</font></td><td><font color=black>M</font></td><td><font color=black>L</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr></table>
 
−
|}
  
−
<br><br>
  
−  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_5_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_5_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs1054374: Ser -> Ile ===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Ser
  
−
|Ile
  
−
|consequences
  
−
|-
  
−
|polar, tiny, hydrophilic, neutral
 
−
|aliphatic, hydrophobic, neutra
  
−
|Ile is much bigger than Ser and also is branched, because it is an aliphatic amino acid. Therefore the structure of both amino acids is really different and Ile is to big for the position where Ser was. Therefore, there has to be a big change in the 3D structure of the protein and the protein probably will loose its function.
 
−
|-
  
−
|}
  
−  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:S293.png|thumb|150px|Amino acid Serine]]
  
−
|[[Image:293I.png|thumb|150px|Amino acid Isoleucine]]
  
−
|[[Image:S293I.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|2
  
−
|38 (Thr)
  
−
|1 (Leu)
  
−
|5
  
−
|9 (Ala, Gly, Pro, Thr)
  
−
|3 (Phe)
  
−
| -2
  
−
|1 (Ala, Asn, Thr)
  
−
| -3 (Trp)
  
−
|-
  
−
|}
  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_6.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...HHHHHHHHCCCEEEECCCCCHHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCCC<font color="red">C</font>C...
  
−
PsiPred:
  
−
...HHHHHHHHCCCEEEECCCCCHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCCCC<font color="red">C</font>H...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:293_mut.png|thumb|250px|Mutation at position 293]]
  
−
| [[Image:293_mut_detail.png|thumb|250px|Mutation at position 293 - detailed view]]
  
−
|}
  
−  
−
'''SNAP Prediction'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|I
  
−
|Neutral
  
−
|2
  
−
|69%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs1054374_SNAP here]]
 
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:293_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=black>w</font></td><td><font color=black>g</font></td><td><font color=red>h</font></td><td><font color=green>y</font></td><td><font color=blue>d</font></td><td><font color=red>r</font></td><td><font color=green>n</font></td><td><font color=black>f</font></td><td><font color=green>q</font></td><td><font color=blue>e</font></td><td><font color=red>k</font></td><td><font color=green>c</font></td><td><font color=black>p</font></td><th>293S</th><td>1.00</td><td><font color=black>M</font></td><td><font color=black>l</font></td><td><font color=black>A</font></td><td><font color=green>S</font></td><td><font color=black>V</font></td><td><font color=green>T</font></td><td><font color=black>I</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr></table>
 
−
|}
  
−
<br><br>
  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_6_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_6_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs121907967: Trp -> TER ===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Trp
  
−
|TER
  
−
|consequences
  
−
|-
  
−
|aromatic, polar, hydrophobic
  
−
|TER
  
−
|By this change, the protein is not complete, therefore it is not possible for the protein to fold and to function.
 
−
|-
  
−
|}
  
−  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:W329.png|thumb|150px|Amino acid Tryptophan]]
  
−
|
  
−
|[[Image:prot_ter.png|thumb|150px|Visualization of the mutated protein]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|X
  
−
|2 (Arg)
  
−
|0 (all, except Arg, Phe, Ser, Tyr)
 
−
|X
  
−
|2 (Arg)
  
−
|0 (all, except Arg, His, Leu, Phe, Ser, Tyr)
  
−
|X
  
−
|2 (Tyr)
  
−
| -4 (Asn, Asp, Pro)
  
−
|-
  
−
|}
  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_6.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...CCCCCCCCC<font color="red">C</font>CCHHHHHHHHHCCCCCCHHHHHHHHHHHHHHHHHHCCCEEEEECC...
  
−
PsiPred:
  
−
...CCCCCCCCC<font color="red">C</font>CCHHHHHHHHHCCCCCCHHHHHHHHHHHHHHHHHHCCCCEEEECC...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:329_mut.png|thumb|250px|Mutation at position 329]]
  
−
| [[Image:329_mut_detail.png|thumb|250px|Mutation at position 329 - detailed view]]
  
−
|}
  
−  
−  
−
'''SNAP Prediction'''
  
−  
−
No prediction available, because the protein ends here.
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907967_SNAP here]]
  
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:329_sift.png.png|center]]
  
−
|}
  
−
<br><br>
  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_7_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_7_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs1800430: Asn -> Asp===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Asn
  
−
|Asp
  
−
|consequences
  
−
|-
  
−
|polar, small, hydrophilic, negatively charged
  
−
|polar, small, hydrophilic, negatively charged
  
−
|Both amino acids have the same properities and therefore we suggest that an exchange of these two amino acids do not destroy the protein structure and function
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:N399.png|thumb|150px|Amino acid Asparagine]]
  
−
|[[Image:399D.png|thumb|150px|Amino acid Aspartic acid]]
  
−
|[[Image:N399D.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|36
  
−
|36 (Asp)
  
−
|0 (Cys, Met)
  
−
|7
  
−
|7 (Asp)
  
−
|2 (Cys, Leu, Phe, Trp)
  
−
|1
  
−
|1 (Asp, His, Ser)
  
−
| -4 (Trp)
  
−
|-
  
−
|}
  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_8.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...CCCCCCCEEEEEECCCCCCC<font color="red">C</font>HHHHHHHHHCCCCEEECCCCCCCCCCCCCCCCCC...
  
−
PsiPred:
  
−
...CCCCCCCCEEEEECCCCCCC<font color="red">H</font>HHHHHHHHHCCCEEEECCCCCCCCCCCCCCCCCC...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:399_mut.png|thumb|250px|Mutation at position 399]]
  
−
| [[Image:399_mut_detail.png|thumb|250px|Mutation at position 399 - detailed view]]
  
−
|}
  
−  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|D
  
−
|Neutral
  
−
|1
  
−
|60%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs1800430_SNAP here]]
  
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:399_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=black>w</font></td><td><font color=green>y</font></td><td><font color=black>f</font></td><td><font color=green>c</font></td><td><font color=black>m</font></td><th>399N</th><td>0.72</td><td><font color=black>i</font></td><td><font color=red>H</font></td><td><font color=black>v</font></td><td><font color=black>l</font></td><td><font color=black>g</font></td><td><font color=black>P</font></td><td><font color=green>t</font></td><td><font color=red>R</font></td><td><font color=blue>D</font></td><td><font color=blue>E</font></td><td><font color=green>Q</font></td><td><font color=black>A</font></td><td><font color=green>S</font></td><td><font color=red>K</font></td><td><font color=green>N</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr></table>
 
−
|}
  
−
<br><br>
  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_8_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_8_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs121907982: Ile -> Val===
  
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Ile
  
−
|Val
  
−
|consequences
  
−
|-
  
−
|aliphatic, hydrophobic, neutra
  
−
|aliphatic, hydrophobic, neutral
 
−
|In this case, the pysicochemical properties are equal. Furthermore, they almost agree in their size. Therefore, we suggest, that there is no big effect on the 3D structure of the protein and therefore, also no big effect on the protein function.
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:I436.png|thumb|150px|Amino acid Isoleucine]]
  
−
|[[Image:436V.png|thumb|150px|Amino acid Valin]]
  
−
|[[Image:I436V.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|33
  
−
|33 (Val)
  
−
|0 (Gly, Pro, Trp)
  
−
|9
  
−
|9 (Val)
  
−
|1 (Trp)
  
−
|3
  
−
|3 (Val)
  
−
| -4 (Gly)
  
−
|-
  
−
|}
  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_9.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...HHHHHHHHCCCCEEECCCCCCCCCCCCCCCCCCCC<font color="red">C</font>CCCCCCCCCCCCCCEEEE...
  
−
PsiPred:
  
−
...HHHHHHHHCCCEEEECCCCCCCCCCCCCCCCCCCC<font color="red">C</font>CCCCCCCCHHHHCCCCCE...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:436_mut.png|thumb|250px|Mutation at position 436]]
  
−
| [[Image:436_mut_detail.png|thumb|250px|Mutation at position 436 - detailed view]]
  
−
|}
  
−  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|V
  
−
|Neutral
  
−
|0
  
−
|53%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907982_SNAP here]]
  
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:436_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=black>w</font></td><td><font color=green>c</font></td><th>436I</th><td>1.00</td><td><font color=black>f</font></td><td><font color=green>Y</font></td><td><font color=red>H</font></td><td><font color=black>M</font></td><td><font color=black>p</font></td><td><font color=black>I</font></td><td><font color=black>V</font></td><td><font color=black>g</font></td><td><font color=black>L</font></td><td><font color=green>n</font></td><td><font color=green>T</font></td><td><font color=green>Q</font></td><td><font color=blue>D</font></td><td><font color=red>R</font></td><td><font color=black>A</font></td><td><font color=green>S</font></td><td><font color=blue>E</font></td><td><font color=red>K</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr>
  
−
</table>
 
−
|}
  
−
<br><br>
  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_9_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_9_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
−  
−
===rs121907968: Trp -> Arg===
 
−  
−
'''pysicochemical properities'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Trp
  
−
|Arg
  
−
|consequences
  
−
|-
  
−
|aromatic, polar, hydrophobic, neutral
  
−
|positive charged, polar, hydrophilic
  
−
|Trp is very big, because of two aromatic rings in its structure. Furthermore, it is hydrophobic, whereas, Arg is a hydrophilic amino acid. Therefore, the changes in the 3D structure might be extreme and delete the function of the protein.
 
−
|-
  
−
|}
  
−  
−
'''Visualisation of the mutation'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|picture original aa
  
−
|picture mutated aa
  
−
|combined picture
  
−
|-
  
−
|[[Image:W485.png|thumb|150px|Amino acid Tryptophan]]
  
−
|[[Image:485R.png|thumb|150px|Amino acid Arginine]]
  
−
|[[Image:W485R.png|thumb|150px|Picture which visualize the mutation]]
  
−
|-
  
−
|}
  
−  
−
'''Subsitution Matrices values'''
  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|colspan="3" | PAM 1
  
−
|colspan="3" | Pam 250
  
−
|colspan="3" | BLOSOUM 62
  
−
|-
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|value aa
  
−
|most frequent substitution
  
−
|rarest substitution
  
−
|-
  
−
|2
  
−
|2 (Arg)
  
−
|0 (all, except Arg, Phe, Ser, Tyr)
 
−
|2
  
−
|2 (Arg)
  
−
|0 (all, except Arg, His, Leu, Phe, Ser, Tyr)
  
−
| -3
  
−
|2 (Tyr)
  
−
| -4 (Asn, Asp, Pro)
  
−
|-
  
−
|}
  
−  
−
'''Conservation analysis with multiple alignments'''
  
−
[[Image:mut_10.png|thumb|center|600px|Mutation in the multiple alignment]]
  
−  
−  
−
'''Secondary structure mutation analysis'''
  
−  
−
JPred:
  
−
...HHHHC<font color="red">C</font>CCCCCCHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCHHHCCC...
  
−
PsiPred:
  
−
...HHHCC<font color="red">C</font>CCCCCCHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCCCCCCC...
  
−  
−
Comparison with the real structure:
  
−
{|
  
−
| [[Image:485_mut.png|thumb|250px|Mutation at position 485]]
  
−
| [[Image:485_mut_detail.png|thumb|250px|Mutation at position 485 - detailed view]]
  
−
|}
  
−  
−
'''SNAP Prediction'''
  
−  
−
{| border="1" style="text-align:center; border-spacing:0;"
  
−
|Substitution
  
−
|Prediction
  
−
|Reliability Index
 
−
|Expected Accuracy
  
−
|-
  
−
|R
  
−
|Non-neutral
  
−
|7
  
−
|96%
  
−
|-
  
−
|}
  
−  
−
A detailed list of all possible substitutions can be found [[http://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/rs121907968_SNAP here]]
  
−  
−
'''SIFT Prediction'''
  
−  
−
SIFT Matrix:<br>
  
−
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
  
−  
−
{|
  
−
| [[Image:sift_legend.png|center]]
  
−
|-
  
−
| [[Image:485_sift.png.png|center]]
  
−
|}
  
−  
−
SIFT Table<br>
  
−
Threshold for intolerance is 0.05.<BR>Amino acid color code: nonpolar, <font color=green>uncharged polar</font>, <font color=red>basic</font>, <font color=blue>acidic</font>. <BR>Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
  
−
<br>
  
−
{| class="wikitable centered"
  
−
|<table cellspacing=0 border=0 width=0 cols=41><th colspan=20 align=center>Predict Not Tolerated</th><BR><th>Position</th><th>Seq Rep</th><BR><th colspan=20 align=center>Predict Tolerated</th>
  
−
<tr><td><font color=gray> </font></td><td><font color=green>y</font></td><td><font color=black>v</font></td><td><font color=green>t</font></td><td><font color=green>s</font></td><td><font color=red>r</font></td><td><font color=green>q</font></td><td><font color=black>p</font></td><td><font color=green>n</font></td><td><font color=black>m</font></td><td><font color=black>l</font></td><td><font color=red>k</font></td><td><font color=black>i</font></td><td><font color=red>h</font></td><td><font color=black>g</font></td><td><font color=black>f</font></td><td><font color=blue>e</font></td><td><font color=blue>d</font></td><td><font color=green>c</font></td><td><font color=black>a</font></td><th>485W</th><td>0.97</td><td><font color=black>W</font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td><td><font color=gray> </font></td></tr>
  
−
</table>
 
−
|}
  
−
<br><br>
  
−  
−
'''Polyphen2 Prediction'''
  
−
{|
  
−
| [[Image:mut_10_humdiv.png|thumb|450px|HumDiv prediction]]
  
−
| [[Image:mut_10_humvar.png|thumb|450px|HumVar prediction]]
  
−
|}
  
   
 
=== Summary page ===
  
=== Summary page ===

Revision as of 17:02, 23 June 2011

Mutations

SNP-id codon number mutation codon mutation triplet
rs4777505 29 Asn -> Ser AAC -> AGC
rs121907979 39 Leu -> Arg CTT -> CGT
rs61731240 179 His -> Asp CAT -> GAT
rs121907974 211 Phe -> Ser TTC -> TCC
rs61747114 248 Leu -> Phe CTT -> TTT
rs1054374 293 Ser -> Ile AGT -> ATT
rs121907967 329 Trp -> TER TGG -> TAG
rs1800430 399 Asn -> Asp AAC -> GAC
rs121907982 436 Ile -> Val ATA -> GTA
rs121907968 485 Trp -> Arg gTGG -> CGG

Analysis of the mutations

We created for each mutation an extra page. The summary of the analysis can be seen in the Summary Section.


Summary page

method  mutations
Asn -> Ser (rs4777505) Leu -> Arg (rs121907979) His -> Asp (rs61731240) Phe -> Ser (rs121907974) Leu -> Phe (rs61747114) Ser -> Ile (rs1054374) Trp -> TER (rs121907967) Asn -> Asp (rs1800430) Ile -> Val (rs121907982) Trp -> Arg (rs121907968)
pysiochemical properitites neutral non-neutral non-neutral non-neutral neutral non-neutral non-neutral neutral neutral non-neutral
visuale analysis todo non-neutral non-neutral non-neutral todo neutral non-neutral todo neutral non-neutral
PAM1 neutral non-neutral non-neutral non-neutral no statement non-neutral no information neutral neutral neutral
PAM250 neutral non-neutral no statement non-neutral no statement no statement no information neutral neutral neutral
BLOSUM62 neutral no statement no statement non-neutral neutral non-neutral no information neutral neutral non-neutral
multiple alignment neutral neutral non-neutral non-neutral non-neutral neutral neutral neutral neutral non-neutral
analysis with Jpred non-neutral non-neutral neutral neutral neutral neutral neutral neutral neutral neutral
analysis with PsiPred non-neutral non-neutral neutral neutral neutral neutral neutral non-neutral neutral neutral
analysis with real structure non-neutral no statement neutral neutral non-neutral neutral non-neutral no statement non-neutral non-neutral
SNAP Prediction neutral non-neutral non-neutral non-neutral neutral neutral no information neutral neutral non-neutral
SIFT Prediction neutral non-neutral non-neutral non-neutral neutral neutral no information neutral neutral non-neutral
PolyPhen2 Prediction neutral non-neutral non-neutral non-neutral neutral neutral no information neutral neutral non-neutral
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