Lab Journal - Task 8 (PAH)

Mutation dataset

For the generation of the mutation dataset the following five SNPs from the HGMD database were used (25th June 2013): <figtable id="mutds_hgmd">

Missense mutations (SNPs) from HGMD
Accession Number	Codon change	Sequence position	Amino acid change	Codon number	Disease	Reference
CM000542	CAG⇒CTG	59	Gln(Q)-Leu(L)	20	Hyperphenylalaninaemia	Hennermann (2000) Hum Mutat 15, 254
CM045080	GGT⇒AGT	307	Gly(G)-Ser(S)	103	Phenylketonuria	Lee (2004) J Hum Genet 49, 617
CM910286	GCC⇒GTC	776	Ala(A)-Val(V)	259	Phenylketonuria	Labrune (1991) Am J Hum Genet 48, 1115
CM010981	AAG⇒ACG	1022	Lys(K)-Thr(T)	341	Phenylketonuria	Tyfield (1997) Am J Hum Genet 60, 388
CM090791	CCA⇒CAA	1247	Pro(P)-Gln(Q)	416	Hyperphenylalaninaemia	Dobrowolski (2009) J Inherit Metab Dis 32, 10

</figtable>

Furthermore, the following five mutations from dbSNP were added (25th June 2013): <figtable id="mutds_dbSNP">

Missense mutations (SNPs) from dbSNP
Reference SNP	Codon change	Sequence position	Amino acid change	Codon number	Disease
rs199475569	CAC⇒AAC	190	His(H)-Asn(N)	64	?
rs199475681	AGA⇒ATA	368	Arg(R)-Ile(I)	123	?
rs62508752	ACA⇒CCA	796	Thr(T)-Ala(A)	266	Phenylketonuria
rs199475695	TTT⇒TCT	1175	Phe(F)-Ser(S)	392	?
rs199475696	ATT⇒ACT	1262	Ile(I)-Thr(T)	421	?

</figtable>

SIFT

• A259V

Substitution at pos 20 from Q to L is predicted to be TOLERATED with a score of 0.16.
   Median sequence conservation: 3.20
   Sequences represented at this position:42

• R123I

Substitution at pos 64 from H to N is predicted to AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

• Q20L

Substitution at pos 103 from G to S is predicted to be TOLERATED with a score of 0.90.
   Median sequence conservation: 3.02
   Sequences represented at this position:72

• G103S

Substitution at pos 123 from R to I is predicted to be TOLERATED with a score of 0.05.
   Median sequence conservation: 3.01
   Sequences represented at this position:76

• H64N

Substitution at pos 259 from A to V is predicted to AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

• I421T

Substitution at pos 266 from T to A is predicted to AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

• K341T

Substitution at pos 341 from K to T is predicted to AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

• F392S

Substitution at pos 392 from F to S is predicted to AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

• P416Q

Substitution at pos 416 from P to Q is predicted to AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.00
   Sequences represented at this position:74

• T266A

Substitution at pos 421 from I to T is predicted to AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.00
   Sequences represented at this position:74

PolyPhen2

• A259V

HumDiv
This mutation is predicted to be probably damaging with a score of 1.000 (sensitivity: 0.00; specificity: 1.00)
HumVar
This mutation is predicted to be probably damaging with a score of 1.000 (sensitivity: 0.00; specificity: 1.00)

• R123I
• Q20L
• G103S
• H64N
• I421T
• K341T
• F392S
• P416Q
• T266A

SNAP

• A259V
• R123I
• Q20L
• G103S
• H64N
• I421T
• K341T
• F392S
• P416Q
• T266A

MutationTaster

• A259V
• R123I
• Q20L
• G103S
• H64N
• I421T
• K341T
• F392S
• P416Q
• T266A