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Table 1 Genotypes observed in French patients with phenylketonuria. Association with clinical phenotypes and response to BH4 loading-test

From: Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness

Genotypes (?: neither mutation found with sequencing nor rearrangement found in MLPA; #: newly described mutation) Number (freq %) Number of BH4-loading tests (responders/non responders) Total BH4 loading test responders Total BH4 loading test non-responders Number of responsive and/or non-responsive patients previously recorded in the BioPKU database for each responsive genotype of the present study Predicted BH4-sensitivity (PRA) according to the literature ([10] except a [9]; b [30]; c.1066-11G > A [2]) Responsiveness as proposed in this manuscript if "Predicted BH4-sensitivity according to the literature" = unk
mHP mPKU cPKU mut1 mut2 mut3 mut1 mut2
c. [1A > G]; [782G > A] p. [Met1Val]; [Arg261Gln] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk Ra (38.5) -   
c. [60G > C]; [473G > A] p. [Gln20His]; [Arg158Gln] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk R (10) -   
c. [60 + 5G > A]#; [1042C > G] p. [?]; [Leu348Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk R (41) -   
c. [115_117delTTC]; [1042C > G] p. [Phe39del]; [Leu348Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (20) R (41) -   
c. [115_117delTTC]; [1315 + 1G > A] p. [Phe39del]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   R (20) NR (0) -   
c. [117C > G]; [785 T > G]# p. [Phe39Leu]; [Val262Gly] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (49) unk -   
c. [117C > G]; [814G > T] p. [Phe39Leu]; [Gly272*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (49) NR (1) -   
c. [117C > G]; [1169A > G] p. [Phe39Leu]; [Glu390Gly] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 no data R (49) R (72.5) -   
c. [143 T > C]; [143 T > C] p. [Leu48Ser]; [Leu48Ser] 3 (1.15) - 2 (2/0) 1 (1/0) 3 (2 mPKU, 1cPKU) 0 37 R; 5 NR R (39) R (39) -   
c. [143 T > C]; [165delT] p. [Leu48Ser]; [Phe55Leufs*6] 2 (0.77) - - 2 (2/0) 2 (cPKU) 0 2 PKU R R (39) unk -   
c. [143 T > C]; [526C > T] p. [Leu48Ser]; [Arg176*] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 no data R (39) NR (1) -   
c. [143 T > C]; [547_548delinsTT]# p. [Leu48Ser]; [Glu183Leu] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (39) unk -   
c. [143 T > C]; [782G > A] p. [Leu48Ser]; [Arg261Gln] 2 (0.77) - - 2 (2/0) 2 (cPKU) 0 22 R; 5 NR R (39) Ra (38,5) -   
c. [143 T > C]; [1045 T > C] p. [Leu48Ser]; [Ser349Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (39) NR (1) -   
c. [143 T > C]; [1055delG] p. [Leu48Ser]; [Gly352Valfs*48] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (39) unk -   NR
c. [143 T > C]; [1066-11G > A] p. [Leu48Ser]; [?] 3 (1.15) - 1 (0/1) 2 (0/2) 0 3 (1 mPKU, 2 cPKU)   R (39) NR (0) -   
c. [143 T > C]; [1162G > A] p. [Leu48Ser]; [Val388Met] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 2 mPKU R R (39) R (27,5) -   
c. [143 T > C]; [442-?_509 + ?del] p. [Leu48Ser]; [Ex5del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (39) unk -   
c. [155delT]#; [781C > T] p. [Leu52Cysfs*9]; [Arg261*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (1) -   
c. [158G > A]; [?] p. [Arg53His]; [?] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0   unk (79) - -   
c. [164 T > C]#; [1066-11G > A] p. [Phe55Ser]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [165delT]; [194 T > C] p. [Phe55Leufs*6]; [Ile65Thr] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk R (25,3) -   
c. [165delT]; [441 + 5G > T] p. [Phe55Leufs*6]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   unk NRb -   
c. [165delT]; [727C > T] p. [Phe55Leufs*6]; [Arg243*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (1) -   
c. [165delT]; [1066-11G > A] p. [Phe55Leufs*6]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [165delT]; [1315 + 1G > A] p. [Phe55Leufs*6]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [168 + 5G > C]; [168 + 5G > C] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [168 + 5G > C]; [782G > A] p. [?]; [Arg261Gln] 2 (0.77) - - 2 (1/1) 1 (cPKU) minus 61 % 1 (cPKU) 3 PKU R; 1 PKU NR unk Ra (38.5) -   
c. [168 + 5G > C]; [1-?_60 + ?del]# p. [?]; [Ex1del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [169G > T]#; [194 T > C] p. [Glu57*]; [Ile65Thr] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk R (25,3) - NR  
c. [194 T > C]; [204A > T] p. [Ile65Thr]; [Arg68Ser] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 2 PKU R; 1 PKU NR R (25.3) R (87) -   
c. [194 T > C]; [331C > T] p. [Ile65Thr]; [Arg111*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) NR (1) -   
c. [194 T > C]; [386A > G] p. [Ile65Thr]; [Asp129Gly] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) R -   
c. [194 T > C]; [473G > A] p. [Ile65Thr]; [Arg158Gln] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) R (10) -   
c. [194 T > C]; [526C > T] p. [Ile65Thr]; [Arg176*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) NR (1) -   
c. [194 T > C]; [782G > A] p. [Ile65Thr]; [Arg261Gln] 3 (1.15) - - 3 (0/3) 0 3 (3 cPKU)   R (25.3) Ra (38,5) -   
c. [194 T > C]; [782G > C] p. [Ile65Thr]; [Arg261Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) unk -   
c. [194 T > C]; [829 T > G] p. [Ile65Thr]; [Tyr277Asp] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   R (25.3) unk (0–12) -   
c. [194 T > C]; [838G > A] p. [Ile65Thr]; [Glu280Lys] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) NR (1.95) -   
c. [194 T > C]; [842C > T] p. [Ile65Thr]; [Pro281Leu] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   R (25.3) NR (1) -   
c. [194 T > C]; [842 + 1G > A] p. [Ile65Thr]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) unk -   
c. [194 T > C]; [844G > A] p. [Ile65Thr]; [Asp282Asn] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) unk (2) -   
c. [194 T > C]; [898G > T] p. [Ile65Thr]; [Ala300Ser] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 2 mHP R R (25.3) R (31) -   
c. [194 T > C]; [912 + 1G > A] p. [Ile65Thr]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) unk -   
c. [194 T > C]; [916A > G] p. [Ile65Thr]; [I306Val] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 2 R R (25.3) unk (12–39) -   
c. [194 T > C]; [932 T > C] p. [Ile65Thr]; [Leu311Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) NR (1) -   
c. [194 T > C]; [1042C > G] p. [Ile65Thr]; [Leu348Val] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 5 PKU R; 1PKU NR R (25.3) R (41) -   
c. [194 T > C]; [1045 T > C] p. [Ile65Thr]; [Ser349Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (25.3) NR (1) -   
c. [194 T > C]; [1066-11G > A] p. [Ile65Thr]; [?] 4 (1.53) - - 4 (0/4) 0 4 (4 cPKU)   R (25.3) NR (0) -   
c. [194 T > C]; [1169A > G] p. [Ile65Thr]; [Glu390Gly] 2 (0.77) - 1 (1/0) 1 (1/0) 2 (mPKU, cPKU) 0 3 PKU R R (25.3) R (72.5) -   
c. [194 T > C]; [1169A > G]; [1171A > G]# p. [Ile65Thr]; ([Glu390Gly)]; [(Ser391Gly)] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0   R (25.3) R (72.5) unk   
c. [194 T > C]; [1208C > T] p. [Ile65Thr]; [Ala403Val] 4 (1.53) 2 (2/0) 1 (0/1) - 2 (2 mHP) 1 (PKUa) minus 15 % 1 mHP R R (25.3) R (32) -   
c. [194 T > C]; [1222C > T] p. [Ile65Thr]; [Arg408Trp] 2 (0.77) - - 2 (1/1) 1 (cPKU) minus 32 % 1 (cPKU) minus 14 % 9 R; 8 NR R (25.3) NR (1) -   
c. [196G > T]#; [1315 + 1G > A] p. [Glu66*]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) - NR  
c. [204A > T]; [204A > T] p. [Arg68Ser]; [Arg68Ser] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 1 mPKU R R (87) R (87) -   
c. [204A > T]; [398_401delATCA] p. [Arg68Ser]; [Asn133Argfs*61] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (87) unk -   
c. [204A > T]; [526C > T]; [707-7A > T] p. [Arg68Ser]; [(Arg176*)]; [(?)] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data R (87) NR (1) unk   
c. [204A > T]; [611A > G] p. [Arg68Ser]; [Tyr204Cys] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   R (87) unk -   
c. [204A > T]; [814G > T] p. [Arg68Ser]; [Gly272*] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 1cPKU R R (87) NR (1) -   
c. [204A > T]; [1045 T > C] p. [Arg68Ser]; [Ser349Pro] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data R (87) NR (1) -   
c. [204A > T]; [1055delG] p. [Arg68Ser]; [Gly352Valfs*48] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   R (87) unk -   NR
c. [204A > T]; [1162G > A] p. [Arg68Ser]; [Val388Met] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data R (87) R (27.5) -   
c. [204A > T]; [1222C > T] p. [Arg68Ser]; [Arg408Trp] 2 (0.77) - 1 (0/1) 1 (0/1) 0 2 (mPKU, cPKU)   R (87) NR (1) -   
c. [204A > T]; [1315 + 1G > A] p. [Arg68Ser]; [?] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   R (87) NR (0) -   
c. [261C > A]; [1065 + 1G > A] p. [Ser87Arg]; [?] 1 (0.38) 1 (0/1) - - 0 1 (mHP, H0 2.4 mg %, minus 8 %)   R (82) unk -   
c. [266_267insC]; [842C > T] p. [Ala90Cysfs*12]; [Pro281Leu] 1 (0.38) - - 1 (1/0) 1 (cPKU) minus 36 % 0 no data unk NR (1) - unclear  
c. [284_286delTCA]; [441 + 5G > T] p. [Ile95del]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NRb -   
c. [284_286delTCA]; [1243G > A] p. [Ile95del]; [Asp415Asn] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data unk R (93) -   
c. [311C > A]; [442-5C > G] p. [Ala104Asp]; [?] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   R (26) R -   
c. [311C > A]; [1222C > T] p. [Ala104Asp]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (26) NR (1) -   
c. [331C > T]; [782G > A] p. [Arg111*]; [Arg261Gln] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) Ra (38.5) -   
c. [331C > T]; [1222C > T] p. [Arg111*]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [434A > T]; [1222C > T] p. [Asp145Val]; [Arg408Trp] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data unk NR (1) - R  
c. [441 + 5G > T]; [441 + 5G > T] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NRb NRb -   
c. [441 + 5G > T]; [473G > A] p. [?]; [Arg158Gln] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   NRb R (10) -   
c. [441 + 5G > T]; [631C > A] p. [?]; [Pro211Thr] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data NRb R (72) -   
c. [441 + 5G > T]; [782G > A] p. [?]; [Arg261Gln] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   NRb Ra (38.5) -   
c. [441 + 5G > T]; [838G > A] p. [?]; [Glu280Lys] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NRb NR (1.95) -   
c. [441 + 5G > T]; [1045 T > G] p. [?]; [Ser349Ala] 1 (0.38) - - 1 (1/0) 1 (cPKU) minus 41 % 0 no data NRb unk -   R
c. [442-2A > C]#; [442-2A > C]# p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [464G > C]; [1223G > A] p. [Arg155Pro]; [Arg408Gln] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk R (49.7) -   
c. [464G > C]; [510-?-706 + ?del] p. [Arg155Pro]; [Ex6del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [472C > T]; [472C > T] p. [Arg158Trp]; [Arg158Trp] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   unk unk -   
c. [472C > T]; [754C > T] p. [Arg158Trp]; [Arg252Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (1) -   
c. [473G > A]; [473G > A] p. [Arg158Gln]; [Arg158Gln] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (10) R (10) -   
c. [473G > A]; [526C > T] p. [Arg158Gln]; [Arg176*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (10) NR (1) -   
c. [473G > A]; [814G > T] p. [Arg158Gln]; [Gly272*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (10) NR (1) -   
c. [473G > A]; [1066-11G > A] p. [Arg158Gln]; [?] 3 (1.15) - - 3 (0/3) 0 3 (3 cPKU)   R (10) NR (0) -   
c. [473G > A]; [1169A > G] p. [Arg158Gln]; [Glu390Gly] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 5 R R (10) R (72.5) -   
c. [473G > A]; [1222C > T] p. [Arg158Gln]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (10) NR (1) -   
c. [473G > A]; [169-?_352 + ?del] p. [Arg158Gln]; [Ex3del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (10) unk -   
c. [473G > T]; [782G > C] p. [Arg158Trp]; [Arg261Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [491 T > C]; [1241A > G] p. [Ile164Thr]; [Tyr414Cys] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data unk Ra (36) -   
c. [493G > A]; [493G > A] p. [Ala165Thr]; [Ala165Thr] 2 (0.77) - - 2 (1/1) 1 (cPKU) minus 36 % 1 (cPKU) minus 0 % no data unk unk - unclear unclear
c. [493G > C]; [1169A > G] p. [Ala165Pro]; [Glu390Gly] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data unk R (72.5) -   
c. [500A > T]; [1066-11G > A] p. [Asn167Ile]; [?] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data unk NR (0) - R  
c. [504C > A]#; [898G > T] p. [Tyr168*]; [Ala300Ser] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data unk R (31) - NR  
c. [506G > A]; [1066-3C > T] p. [Arg169His]; [?] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data unk R -   
c. [509 + 1G > A]; [561G > A] p. [?]; [Trp187*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [529G > C]; [561G > A] p. [Val177Leu]; [Trp187*] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data unk NR (0) - R  
c. [569 T > C]; [796A > C]# p. [Val190Ala]; [Thr266P] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (110) unk -   
c. [580_581delCT]; [1042C > G] p. [Leu194Glufs*5]; [Leu348Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk R (41) -   
c. [581 T > C]; [842C > T] p. [Leu194Pro]; [Pro281Leu] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   unk NR (1) -   
c. [593_614del22]; [969 + 1G > A] p. [Tyr198Cysfs*136]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [631C > A]; [782G > A] p. [Pro211Thr]; [Arg261Gln] 2 (0.77) - 1 (1/0) 1 (1/0) 2 (mPKU, cPKU) 0 4 mHP R R (72) Ra (38,5) -   
c. [631C > A]; [1066-11G > A] p. [Pro211Thr]; [?] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 10 R R (72) NR (0) -   
c. [632delC]; [1066-11G > A] p. [Pro211Hisfs*130]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [635 T > C]; [1066-11G > A] p. [Leu212Pro]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [638 T > C]; [638 T > C] p. [Leu213Pro]; [Leu213Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [638 T > C]; [727C > T] p. [Leu213Pro]; [Arg243*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (1) -   
c. [648C > G]; [838G > A] p. [Tyr216*]; [Glu280Lys] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (1.95) - NR  
c. [653G > T]; [809G > A] p. [Gly218Val]; [Arg270Lys] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (2.1) -   
c. [653G > T]; [1066-11G > A] p. [Gly218Val]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [663_664delAG]; [912 + 1G > A] p. [Asp222*]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) unk -   
c. [671 T > C]; [671 T > C] p. [Ile224Thr]; [Ile224Thr] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   unk unk -   
c. [682G > A]#; [1066-11G > A] p. [Glu228Lys]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [721C > T]; [931_932delCT]# p. [Arg241Cys]; [Leu311Glyfs*4] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   R (25) unk -   
c. [722G > A]; [722G > A] p. [Arg241His]; [Arg241His] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data R (23) R (23) -   
c. [722G > A]; [782G > A] p. [Arg241His]; [Arg261Gln] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data R (23) Ra (38,5) -   
c. [722G > A]; [838_842 + 3del8] p. [Arg241His]; [His280*] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data R (23) unk -   NR
c. [722G > A]; [842 + 1G > A] p. [Arg241His]; [?] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data R (23) unk -   
c. [722G > A]; [1066-11G > A] p. [Arg241His]; [?] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data R (23) NR (0) -   
c. [727C > T]; [727C > T] p. [Arg243*]; [Arg243*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [727C > T]; [842C > T] p. [Arg243*]; [Pro281Leu] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [727C > T]; [912 + 1G > A] p. [Arg243*]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) unk -   
c. [727C > T]; [1042C > G] p. [Arg243*]; [Leu348Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) R (41) -   
c. [727C > T]; [1066-11G > A] p. [Arg243*]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (0) -   
c. [727C > T]; [?] p. [Arg243*]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) - -   
c. [728G > A]; [913-7A > G] p. [Arg243Gln]; [?] 1 (0.38) - - - 0 1 (unk)   R (23) unk -   
c. [728G > A]; [912 + 1G > A] p. [Arg243Gln]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   R (23) unk -   
c. [728G > A]; [1055delG] p. [Arg243Gln]; [Gly352Valfs*48] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   R (23) unk -   NR
c. [728G > A]; [1208C > T] p. [Arg243Gln]; [Ala403Val] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 6 mHP R R (23) R (32) -   
c. [734 T > C]; [1315 + 1G > A] p. [Val245Ala]; [?] 1 (0.38) 1 (0/1) - - 0 1 (mHP, H0 2.4 mg %, minus 4 %)   R (50) NR (0) -   
c. [754C > T]; [838G > A] p. [Arg252Trp]; [Glu280Lys] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1.95) -   
c. [754C > T]; [838_842 + 3del8] p. [Arg252Trp]; [His280*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) unk -   NR
c. [754C > T]; [1042C > G] p. [Arg252Trp]; [Leu348Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) R (41) -   
c. [754C > T]; [1045 T > G] p. [Arg252Trp]; [Ser349Ala] 1 (0.38) - 1 (1/0) - 1 (mPKU) minus 51 % 0 no data NR (1) unk -   R
c. [754C > T]; [1055delG] p. [Arg252Trp]; [Gly352Valfs*48] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) unk -   NR
c. [754C > T]; [1066-11G > A] p. [Arg252Trp]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (0) -   
c. [754C > T]; [1208C > T] p. [Arg252Trp]; [Ala403Val] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 3 R NR (1) R (32) -   
c. [754C > T]; [1241A > G] p. [Arg252Trp]; [Tyr414Cys] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 4 R NR (1) Ra (36) -   
c. [755G > A]; [782G > A] p. [Arg252Gln]; [Arg261Gln] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 no data unk (3–24) Ra (38,5) -   
c. [755G > A]; [1066-11G > A] p. [Arg252Gln]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk (3–24) NR (0) -   
c. [770G > A]; [932 T > C] p. [Gly257Asp]; [Leu311Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (1) -   
c. [776C > T]; [1066-11G > A] p. [Ala259Val]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   unk (2) NR (0) -   
c. [776C > T]; [1222C > T] p. [Ala259Val]; [Arg408Trp] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   unk (2) NR (1) -   
c. [776C > T]; [970-?_1359 + ?]# p. [Ala259Val]; [Ex10_13del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk (2) unk -   
c. [781C > G]#; [913-7A > G] p. [Arg261Gly]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [781C > T]; [781C > T] p. [Arg261*]; [Arg261*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [781C > T]; [782G > A] p. [Arg261*]; [Arg261Gln] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) Ra (38.5) -   
c. [781C > T]; [1222C > T] p. [Arg261*]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [782G > A]; [782G > A] p. [Arg261Gln]; [Arg261Gln] 8 (3.065) - - 8 (6/2) 6 (cPKU) 2 (cPKU) 59 R; 11 NR Ra (38,5) Ra (38,5) -   
c. [782G > A]; [782G > C] p. [Arg261Gln]; [Arg261Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (38,5) unk -   
c. [782G > A]; [814G > T] p. [Arg261Gln]; [Gly272*] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   Ra (38,5) NR (1) -   
c. [782G > A]; [838G > A] p. [Arg261Gln]; [Glu280Lys] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (38,5) NR (1.95) -   
c. [782G > A]; [842 + 1G > A] p. [Arg261Gln]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   Ra (38,5) unk -   
c. [782G > A]; [912 + 1G > A] p. [Arg261Gln]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (38,5) unk -   
c. [782G > A]; [1045 T > C] p. [Arg261Gln]; [Ser349Pro] 2 (0.77) - - 2 (1/1) 1 (cPKU) minus 41 % 1 (cPKU) minus 20 % 3 R Ra (38,5) NR (1) -   
c. [782G > A]; [1055delG] p. [Arg261Gln]; [Gly352Valfs*48] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (38,5) unk -   NR
c. [782G > A]; [1066-11G > A] p. [Arg261Gln]; [?] 4 (1.53) - - 4 (0/4) 0 4 (4 cPKU)   Ra (38,5) NR (0) -   
c. [782G > A]; [1068C > G] p. [Arg261Gln]; [Tyr356*] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (38,5) NR (1) -   
c. [782G > A]; [1162G > A] p. [Arg261Gln]; [Val388Met] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (38,5) R (72.5) -   
c. [782G > A]; [1208C > T] p. [Arg261Gln]; [Ala403Val] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 6 mHP R Ra (38,5) R (32) -   
c. [782G > A]; [1222C > T] p. [Arg261Gln]; [Arg408Trp] 4 (1.53) - 1 (0/1) 3 (0/3) 0 4 (1 mPKU, 3 cPKU)   Ra (38,5) NR (1) -   
c. [782G > A]; [1241A > G] p. [Arg261Gln]; [Tyr414Cys] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 12 R Ra (38,5) Ra (38,5) -   
c. [782G > A]; [1315 + 1G > A] p. [Arg261Gln]; [?] 5 (1.915) - - 5 (0/5) 0 5 (5 cPKU)   Ra (38,5) NR (0) -   
c. [782G > A]; [510-?-706 + ?del] p. [Arg261Gln]; [Ex6del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (38,5) unk -   
c. [782G > C]; [1241A > G] p. [Arg261Pro]; [Tyr414Cys] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 2 PKU R; 1 PKU NR unk Ra (36) -   
c. [782G > C]; [1315 + 1G > A] p. [Arg261Pro]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [812A > G]; [1222C > T] p. [His271Arg]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (1) -   
c. [814G > T]; [1042C > G] p. [Gly272*]; [Leu348Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) R (41) -   
c. [814G > T]; [1045 T > C] p. [Gly272*]; [Ser349Pro] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [814G > T]; [1066-11G > A] p. [Gly272*]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (0) -   
c. [814G > T]; [1162G > A] p. [Gly272*]; [Val388Met] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 no data NR (1) R (27.5) -   
c. [814G > T]; [1169A > G] p. [Gly272*]; [Glu390Gly] 2 (0.77) - 2 (2/0) - 2 (mPKU) 0 2 R NR (1) R (72.5) -   
c. [814G > T]; [1208C > T] p. [Gly272*]; [Ala403Val] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data NR (1) R (32) -   
c. [814G > T]; [1222C > T] p. [Gly272*]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [829 T > G]; [1042C > G] p. [Tyr277Asp]; [Leu348Val] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data unk (0–12) R (41) -   
c. [829 T > G]; [1066-11G > A] p. [Tyr277Asp]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk (0–12) NR (0) -   
c. [833C > A]; [1315 + 1G > A] p. [Thr278Asn]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [837delC]#; [1315 + 1G > A] p. [His280Asnfs*61]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [838G > A]; [838G > A] p. [Glu280Lys]; [Glu280Lys] 11 (4.21) - - 11 (0/11) 0 11 (11 cPKU)   NR (1.95) NR (1.95) -   
c. [838G > A]; [842 + 1G > A] p. [Glu280Lys]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1.95) unk -   
c. [838G > A]; [869A > T]# p. [Glu280Lys]; [His290Leu] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1.95) unk -   
c. [838G > A]; [898G > T] p. [Glu280Lys]; [Ala300Ser] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data NR (1.95) R (31) -   
c. [838G > A]; [1055delG] p. [Glu280Lys]; [Gly352Valfs*48] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1.95) unk -   NR
c. [838G > A]; [1066-11G > A] p. [Glu280Lys]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1.95) NR (0) -   
c. [838G > A]; [1066-3C > T] p. [Glu280Lys]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   NR (1.95) R -   
c. [838G > A]; [1208C > T] p. [Glu280Lys]; [Ala403Val] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data NR (1.95) R (32) -   
c. [838G > A]; [1222C > T] p. [Glu280Lys]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1.95) NR (1) -   
c. [838G > A]; [1243G > A] p. [Glu280Lys]; [Asp415Asn] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data NR (1.95) R (93) -   
c. [841C > T]; [1315 + 1G > A] p. [Pro281Ser]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [842 + 1G > A]; [1066-11G > A] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [842 + 3G > C]; [842 + 3G > C] p. [?]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   unk unk -   
c. [842C > T]; [842C > T] p. [Pro281Leu]; [Pro281Leu] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   NR (1) NR (1) -   
c. [842C > T]; [898G > T] p. [Pro281Leu]; [Ala300Ser] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 3 R NR (1) R (31) -   
c. [842C > T]; [926C > T] p. [Pro281Leu]; [A309Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) R (44) -   
c. [842C > T]; [1042C > G] p. [Pro281Leu]; [Leu348Val] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   NR (1) R (41) -   
c. [842C > T]; [1066-11G > A] p. [Pro281Leu]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (0) -   
c. [842C > T]; [1222C > T] p. [Pro281Leu]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) NR (1) -   
c. [842C > T]; [1241A > G] p. [Pro281Leu]; [Tyr414Cys] 2 (0.77) - 1 (1/0) 1 (1/0) 2 (mPKU, cPKU) 0 6 R; 1 NR NR (1) Ra (36) -   
c. [842C > T]; [1315 + 1G > A] p. [Pro281Leu]; [?] 3 (1.15) - - 3 (1/2) 1 (cPKU) minus 33 % 2 (2 cPKU) 6 cPKU NR NR (1) NR (0) -   
c. [887A > G]#; [1222C > T] p. [Asp296Gly]; [Arg408Trp] 1 (0.38) - - 1 (1/0) 1 (cPKU) minus 36 % 0 no data unk NR (1) - unclear  
c. [896 T > G]; [1222C > T] p. [Phe299Cys]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk (3) NR (1) -   
c. [896 T > G]; [169-?_352 + ?del] p. [Phe299Cys]; [Ex3del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk (3) unk -   
c. [898G > T]; [1045 T > C] p. [Ala300Ser]; [Ser349Pro] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 4 R R (31) NR (1) -   
c. [898G > T]; [1066-11G > A] p. [Ala300Ser]; [?] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 16 R R (31) NR (0) -   
c. [898G > T]; [1315 + 1G > A] p. [Ala300Ser]; [?] 2 (0.77) 2 (2/0) - - 2 (mHP) 0 3 R R (31) NR (0) -   
c. [912 + 1G > A]; [1055delG] p. [?]; [Gly352Valfs*48] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   NR
c. [912 + 1G > A]; [1315 + 1G > A] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [912 + 2 T > C]#; [1042C > G] p. [?]; [Leu348Val] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk R (41) -   
c. [913-8A > G]#; [1315 + 1G > A] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk NR (0) -   
c. [1042C > G]; [1042C > G] p. [Leu348Val]; [Leu348Val] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 3 PKU R R (41) R (41) -   
c. [1042C > G]; [1066-11G > A] p. [Leu348Val]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (41) NR (0) -   
c. [1042C > G]; [1169A > G] p. [Leu348Val]; [Glu390Gly] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 3 R R (41) R (72.5) -   
c. [1042C > G]; [1222C > T] p. [Leu348Val]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (41) NR (1) -   
c. [1045 T > C]; [1066-3C > T] p. [Ser349Pro]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) R -   
c. [1045 T > C]; [1162G > A] p. [Ser349Pro]; [Val388Met] 2 (0.77) - - 2 (1/1) 1 (cPKU) minus 72 % 1 (cPKU) minus 20 % 2 R; 4 cPKU NR NR (1) R (27.5) -   
c. [1045 T > C]; [1169A > G] p. [Ser349Pro]; [Glu390Gly] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 5 R NR (1) R (72.5) -   
c. [1045 T > C]; [1243G > A] p. [Ser349Pro]; [Asp415Asn] 1 (0.38) 1 (0/1) - - 0 1 (mHP)   NR (1) R (93) -   
c. [1045 T > C]; [442-?_509 + ?del] p. [Ser349Pro]:Ex5del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (1) unk -   
c. [1045 T > G]; [1045 T > G] p. [Ser349Ala]; [Ser349Ala] 2 (0.77) - 1 (1/0) 1 (0/1) 1 (mPKU) minus 71.5 % 1 (cPKU) minus 7 % 1 R unk unk - R R
c. [1055delG]; [1055delG] p. [Gly352Valfs*48]; [Gly352Valfs*48] 7 (2.68) - - 7 (0/7) 0 7 (7 cPKU)   unk unk - NR NR
c. [1055delG]; [1066-11G > A] p. [Gly352Valfs*48]; [?] 2 (0.77) - - 2 (0/2) 0 2 (2 cPKU)   unk NR (0) - NR  
c. [1055delG]; [1208C > T] p. [Gly352Valfs*48]; [Ala403Val] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data unk R (32) - NR  
c. [1065 + 1G > A]; [1169A > G] p. [?]; [Glu390Gly] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data unk R (72.5) -   
c. [1066-2A > T]#; [1169A > G] p. [Glu390Gly]; [?] 1 (0.38) - - - 1 ('unk) 0 no data unk R (72.5) -   
c. [1066-11G > A]; [1066-11G > A] p. [?]; [?] 5 (1.915) - 1 (0/1) 4 (1/3) 1 (cPKU) minus 31 % 4 (1 mPKU, 3 cPKU) 10 R; 74 NR NR (0) NR (0) -   
c. [1066-11G > A]; [1162G > A] p. [?]; [Val388Met] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (0) R (27.5) -   
c. [1066-11G > A]; [1196 T > C]# p. [?]; [Val399Ala] 1 (0.38) - - 1 (1/0) 1 (cPKU) minus 97 % 0 no data NR (0) unk -   R
c. [1066-11G > A]; [1199 + 1G > C] p. [?]; [?] 3 (1.15) - 1 (0/1) 2 (1/1) 1 (cPKU) minus 37.5 % 2 (mPKU, cPKU) no data NR (0) unk -   unclear
c. [1066-11G > A]; [1222C > T] p. [?]; [Arg408Trp] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (0) NR (1) -   
c. [1066-11G > A]; [1223G > A] p. [?]; [Arg408Gln] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 no data NR (0) R (49.7) -   
c. [1066-11G > A]; [1241A > G] p. [?]; [Tyr414Cys] 4 (1.53) - 4 (3/1) - 3 (mPKU) 1 (mPKU) minus 21 % 18 R; 2 NR NR (0) Ra (36) -   
c. [1066-11G > A]; [1315 + 1G > A] p. [?]; [?] 3 (1.15) - - 3 (0/3) 0 3 (3 cPKU)   NR (0) NR (0) -   
c. [1066-11G > A]; [510-?_706 + ?dup]# p. [?]; [Ex6dup] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   NR (0) unk -   
c. [1066-11G > A]; [?] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (0) - -   
c. [1066-3C > T]; [1180G > T]# p. [?]; [Asp394Tyr] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   R unk -   
c. [1068C > G]; [1162G > A] p. [Tyr356*]; [Val388Met] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 no data NR (1) R (27.5) -   
c. [1139C > T]; [1180G > T]# p. [Thr380Met]; [Asp394Tyr] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data R unk -   
c. [1139C > T]; [1-?_60 + ?del]# p. [Thr380Met]; [Ex1del] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data R unk -   
c. [1162G > A]; [1162G > A] p. [Val388Met]; [Val388Met] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   R (27.5) R (27.5) -   
c. [1162G > A]; [1169A > G] p. [Val388Met]; [Glu390Gly] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 8 R R (27.5) R (72.5) -   
c. [1162G > A]; [1223G > A] p. [Val388Met]; [Arg408Gln] 1 (0.38) - - 1 (1/0) 1 (cPKU) 0 no data R (27.5) R (49,7) -   
c. [1163 T > C]#; [1208C > T] p. [Val388Ala]; [Ala403Val] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data unk R (32) -   
c. [1169A > G]; [1241A > G] p. [Glu390Gly]; [Tyr414Cys] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 no data R (72.5) Ra (36) -   
c. [1169A > G]; [?] p. [Glu390Gly]; [?] 1 (0.38) 1 (1/0) - - 1 (mHP) 0   R (72.5) - -   
c. [1199 + 1G > C]; [1199 + 1G > C] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   unk unk -   
c. [1208C > T]; [1222C > T] p. [Ala403Val]; [Arg408Trp] 2 (0.77) 1 (1/0) 1 (1/0) - 2 (mHP, mPKU) 0 6 R R (32) NR (1) -   
c. [1208C > T]; [1315 + 1G > A] p. [Ala403Val]; [?] 1 (0.38) 1 (1/0) - - 1 (mHP) 0 9 R R (32) NR (0) -   
c. [1222C > T]; [1222C > T] p. [Arg408Trp]; [Arg408Trp] 5 (1.915) - - 5 (0/5) 0 5 (5 cPKU)   NR (1) NR (1) -   
c. [1222C > T]; [1223G > A] p. [Arg408Trp]; [Arg408Gln] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data NR (1) R (49.7) -   
c. [1222C > T]; [1241A > G] p. [Arg408Trp]; [Tyr414Cys] 5 (1.915) - 4 (2/2) 1 (0/1) 2 (mPKU) minus 43 %, minus 66 % 3 (2 mPKU, 1cPKU) 30 R; 6 NR NR (1) Ra (36) -   
c. [1222C > T]; [1315 + 1G > A] p. [Arg408Trp]; [?] 3 (1.15) - - 3 (0/3) 0 3 (3 cPKU)   NR (1) NR (0) -   
c. [1222C > T]; [?] p. [Arg408Trp]; [?] 1 (0.38) - 1 (0/1) - 0 1 (mPKU)   NR (1) - -   
c. [1223G > A]; [1241A > G] p. [Arg408Gln]; [Tyr414Cys] 2 (0.77) 1 (1/0) - 1 (1/0) 2 (mHP, cPKU) 0 6 R R (49.7) Ra (38,5) -   
c. [1241A > G]; [1315 + 1G > A] p. [Tyr414Cys]; [?] 3 (1.15) - 1 (1/0) 2 (1/1) 2 (mPKU, cPKU) minus 34 %, minus 39 % 1 (cPKU) minus 21 % 24 PKU R; 1 PKU NR Ra (36) NR (0) -   
c. [1241A > G]; [169-?_352 + ?del] p. [Tyr414Cys]; [Ex3del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   Ra (36) unk -   
c. [1243G > A]; [169-?_352 + ?del] p. [Asp415Asn]; [Ex3del] 1 (0.38) - 1 (1/0) - 1 (mPKU) 0 no data R (93) unk -   
c. [1249 T > A]; [1315 + 1G > A] p. [Tyr417Asn]; [?] 1 (0.38) - 1 (1/0) - 1 (mPKU) minus 37 % 0 no data unk NR (0) - unclear  
c. [1315 + 1G > A]; [1-?_60 + ?del]# p. [?]; [Ex1del] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   NR (0) unk -   
c. [?]; [?] p. [?]; [?] 1 (0.38) - - 1 (0/1) 0 1 (cPKU)   - - -   
  1. Freq frequency, MLPA multiplex ligation-dependent probe amplification, mut mutation, NR non responsive, PRA predicted residual activity, R responsive, unclear BH4-response rate comprised between 30 and 40 %, unk unknown, * indicates a stop codon