Sequence-based mutation analysis HEXA

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

pysicochemical properities

SNP-id	mutation codon	aa propensity	consequences
rs4777505	Asn -> Ser	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.
rs121907979	Leu -> Arg	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.
rs61731240	His -> Asp	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.
rs121907974	Phe -> Ser	aromatic, hydrophobic, neutral -> polar, tiny, hydrophilic, neutral	Phe is much bigger than Ser and also contains an aromatic ring. Furthermore, Phe is hydrophobic, whereas Ser is hydrophilic. Because of this, the structure of the protein will change surely and we suggest, that the protein will not work any longer.
rs61747114	Leu -> Phe	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.
rs1054374	Ser -> Ile	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.
rs121907967	Trp -> TER	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.
rs1800430	Asn -> Asp	polar, small, hydrophilic, negatively charged -> negative charged, small, polar, hydrophilic	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
rs121907982	Ile -> Val	aliphatic, hydrophobic, neutral -> 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.
rs121907968	Trp -> Arg	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 mutations

SNP-id	mutation codon	picture original aa	picture mutated aa	combined picture
rs4777505	Asn -> Ser	Amino acid Asparagine	Amino acid Serine	Picture which visualize the mutation
rs121907979	Leu -> Arg	Amino acid Leucine	Amino acid Arginine	Picture which visualize the mutation
rs61731240	His -> Asp	Amino acid Histidine	Amino acid Aspartate	Picture which visualize the mutation
rs121907974	Phe -> Ser	Amino acid Phenylalanine	Amino acid Serine	Picture which visualize the mutation
rs61747114	Leu -> Phe	Amino acid Leucine	Amino acid Phenylalanine	Picture which visualize the mutation
rs1054374	Ser -> Ile	Amino acid Serine	Amino acid Isoleucine	Picture which visualize the mutation
rs121907967	Trp -> TER	Amino acid Tryptophan		Visualization of the mutated protein
rs1800430	Asn -> Asp	Amino acid Asparagine	Amino acid Aspartic acid	Picture which visualize the mutation
rs121907982	Ile -> Val	Amino acid Isoleucine	Amino acid Valin	Picture which visualize the mutation
rs121907968	Trp -> Arg	Amino acid Tryptophan	Amino acid Arginine	Picture which visualize the mutation

Substitutions Matrices

SNP-id	mutation codon	PAM 1			Pam 250			BLOSOUM 62
		value aa	most frequent substitution	rarest substitution	value aa	most frequent substitution	rarest substitution	value aa	most frequent substitution	rarest substitution
rs4777505	Asn -> Ser	20	36 (Asp)	0 (Cys, Met)	5	7 (Asp)	2 (Cys, Leu, Phe, Trp)	1	1 (Asp, His, Ser)	-4 (Trp)
rs121907979	Leu -> Arg	1	22 (Ile)	0 (Asp, Cys)	4	20 (Met)	2 (Cys)	-2	0 (Phe)	-4 (Asp, Gly)
rs61731240	His -> Asp	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)
rs121907974	Phe -> Ser	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)
rs61747114	Leu -> Phe	13	45 (Met)	0 (Asp, Cys)	13	20 (Met)	2 (Cys)	0	2 (Ile, Met)	-4 (Asp, Gly)
rs1054374	Ser -> Ile	2	38 (Thr)	1 (Leu)	5	9 (Ala, Gly, Pro, Thr)	3 (Phe)	-2	1 (Ala, Asn, Thr)	-3 (Trp)
rs121907967	Trp -> TER	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)
rs1800430	Asn -> Asp	36	36 (Asp)	0 (Cys, Met)	7	7 (Asp)	2 (Cys, Leu, Phe, Trp)	1	1 (Asp, His, Ser)	-4 (Trp)
rs121907982	Ile -> Val	33	33 (Val)	0 (Gly, Pro, Trp)	9	9 (Val)	1 (Trp)	3	3 (Val)	-4 (Gly)
rs121907968	Trp -> Arg	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)