15618328 |
5'UTR |
Silent |
c.1-34C>T |
|
Benign |
unknown |
Procter et al, unpublished |
 Seen with c.566A>G,p.D189G. |
15651988 |
Exon 02 |
Indel |
c.98_104delinsTCC |
p.C33Ffs*36 |
Pathogenic |
yes |
Pomponio (1997a) |
|
15651988;15652102 |
Exon 02;Exon 02 |
Indel; Missense |
c.98_104delinsTCC;212T>C |
p.C33Ffs*36; p.L71P |
Pathogenic;Pathogenic |
unknown |
Wolf (2005) |
 These 2 pathogenic variations, p.C33fs; p.L71P, were observed both in haplotype and alone. |
15651989 |
Exon 02 |
Slient |
c.99C>T |
p.C33C |
Benign |
no |
Wolf (2005) |
|
15651990 |
Exon 02 |
Missense |
c.100G>A |
p.G34S |
Pathogenic |
yes |
Pomponio (1997c) |
 Originally also suspected of being a splice site variant. |
15652018 |
Exon 02 |
Missense |
c.128A>G |
p.H43R |
Uncertain |
unknown |
Procter (2016) |
 No enzyme activity available. Seen with c.1330G>C,p.D444H. |
15652023 |
Exon 02 |
Missense |
c.133G>A |
p.G45R |
Pathogenic |
yes |
Neto (2004) |
|
15652023;15661232 |
Exon 02; Exon 04 |
Missense;Missense |
c.133G>A; 865G>C |
p.G45R; A289P |
Pathogenic |
unknown |
Norrgard (1999) |
 These 2 pathogenic variations, p.G45R; A289P, were observed in haplotype. |
15652023;15661638 |
Exon 02; Exon 04 |
Missense;Missense |
c.133G>A; 1271G>C |
p.G45R; C424S |
Pathogenic |
unknown |
Wolf (2005) |
 These 2 pathogenic variations, p.G45R; C424S, were observed both in haplotype and alone. |
15652026 |
Exon 02 |
Nonsense |
c.136G>T |
p.E46X |
Pathogenic |
unknown |
Milankovics (2007) |
|
15652049;15652050 |
Exon 02 |
Missense;Nonsense |
c.159C>A;160G>T |
p.H53Q;p.E54X |
Pathogenic |
yes |
Wolf (2005) |
 These 2 pathogenic variations, p.H53Q;p.E54X, were observed in haplotype. |
15652061 |
Exon 02 |
Nonsense |
c.171T>G |
p.Y57X |
Pathogenic |
yes |
Pomponio (2000a) |
|
15652074 |
Exon 02 |
Missense |
c.184G>T |
p.V62L |
Pathogenic |
unknown |
Norrgard (1999) |
|
15652074 |
Exon 02 |
Missense |
c.184G>A |
p.V62M |
Pathogenic |
yes |
Muhl (2001) |
|
15652080 |
Exon 02 |
Missense |
c.190G>A |
p.E64K |
Pathogenic |
yes |
Wolf (2002) |
|
15652082 |
Exon 02 |
Missense |
c.192G>C |
p.E64D |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.7U/L. Seen with c.1330G>C,p.D444H. |
15652084 |
Exon 02 |
Insertion |
c.202-205dupATCC |
p.H65fs |
Pathogenic |
yes |
Sivri (2007) |
|
15652084 |
Exon 02 |
Missense |
c.194A>G |
p.H65R |
Pathogenic |
unknown |
Sarafoglou (2009) |
|
15652101 |
Exon 02 |
Slient |
c.211C>T |
p.L71L |
Benign |
unknown |
Ohlsson (2010) |
|
15652102 |
Exon 02 |
Missense |
c.212T>C |
p.L71P |
Pathogenic |
unknown |
Wolf (2005) |
|
15652102;15652126 |
Exon 02;Exon 02 |
Missense;Missense |
c.212T>C;236G>A |
p.L71P;R79H |
Pathogenic |
yes |
Laszlo (2003) |
 These 2 pathogenic variations, p.L71P;R79H, were observed both in haplotype and alone. |
15652113 |
Exon 02 |
Deletion |
c.223delG |
p.A75Lfs*12 |
Pathogenic |
unknown |
|
 Enzyme activity @ 1.5 nmol/ml. Caucasian. |
15652124 |
Exon 02 |
Slient |
c.234C>T |
p.S78S |
Benign |
unknown |
Hymes (2001) |
|
15652125 |
Exon 02 |
Missense |
c.235C>T |
p.R79C |
Pathogenic |
yes |
Pomponio (2000a) |
|
15652125;15660837 |
Exon 02; Exon 04 |
Missense;Missense |
c.235C>T;470G>A |
p.R79C;R157H |
Pathogenic |
yes |
Baykal (2005) |
 These 2 pathogenic variations, p.R79C;R157H, were observed both in haplotype and alone. |
15652125;15661728 |
Exon 02; Exon 04 |
Missense;Missense |
c.235C>T;1361A>C |
p.R79C;Y454C |
Pathogenic |
yes |
Wolf (2005) |
 These 2 sequence variants, p.R79C;Y454C have been observed in haplotype. |
15652126 |
Exon 02 |
Missense |
c.236G>A |
p.R79H |
Pathogenic |
unknown |
Neto (2004) |
|
15652135 |
Exon 02 |
Missense |
c.245C>A |
p.A82D |
Pathogenic |
unknown |
Laszlo (2003) |
|
15652135 |
Exon 02 |
Missense |
c.245C>T |
p.A82V |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 0.5 U/L w/no pair control. Seen with c.1330G>C,p.D444H. |
15652136 |
Exon 02 |
Deletion |
c.246_254del |
p.L83-L85del |
Pathogenic |
yes |
Pomponio (1997a) |
|
15652138 |
Exon 02 |
Missense |
c.248T>C |
p.L83S |
Pathogenic |
unknown |
Ohlsson (2010) |
|
15652147 |
Exon 02 |
Missense |
c.257T>G |
p.M86R |
Pathogenic |
yes |
Li (2014) |
 Enzyme activity @ 1.7 U/L. Seen with c.1368A>C;p.Q456H. |
15652151 |
Exon 02 |
Missense |
c.261C>T |
p.N87N |
Benign |
unknown |
Procter et al, unpublished |
 Seen with c.895G>C,p.A299P and c.1330G>C,p.D444H. |
15652152 |
Exon 02 |
Nonsense |
c.262C>T |
p.Q88X |
Pathogenic |
yes |
Pomponio (1997a) |
|
15652168 |
Exon 02 |
Missense |
c.278A>G |
p.Y93C |
Pathogenic |
yes |
Wolf (2002) |
|
15652188 |
Exon 02 |
Missense |
c.298G>A |
p.A100T |
Pathogenic |
yes |
Wolf (2002) |
|
15652189 |
Exon 02 |
Missense |
c.299C>T |
p.A100V |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.0 U/L. Seen with c.1330G>C,p.D444H. |
15652153 |
Exon 02 |
Deletion |
c.263delA |
p.Q88Rfs*10 |
Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 1.3, 2.7, 1.7 U/L. Seen with c.1330G>C,p.D444H. Abnormal NB screen. |
15652159 |
Exon 02 |
Missense |
c.269T>G |
p.L90R |
Likely Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 1.6U/L. Seen with c.1330G>C,p.D444H. Abnormal NB screen. |
15652173 |
Exon 02 |
Nonsense |
c.283C>T |
p.Q95X |
Pathogenic |
yes |
Wolf (2005) |
 Observed in a patient with c.1330G>C. When observed alone D444H is considered a mild mutation. |
15658419 |
Exon 03 |
Missense |
c.310G>T |
p.D104Y |
Pathogenic |
unknown |
Norrgard (1999) |
|
15658419 |
Intron 02 |
mRNA expression |
c.310-15delT |
Intronic |
Pathogenic |
no |
Li (2014) |
 Enzyme activity @ 1.8 U/L. Seen with c.626G>A;p.R209H. |
15658430 |
Exon 03 |
Missense |
c.321T>G |
p.I107M |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 3.1 U/L. Seen with c.1330G>C,p.D444H. |
15658432 |
Exon 03 |
Insertion |
c.323-324dupTA |
p.V109X |
Pathogenic |
yes |
Tiar (2014) |
|
15658435 |
Exon 03 |
Insertion |
c.326dupT |
p.F110Vfs*42 |
Pathogenic-partial |
unknown |
Procter (2016) |
 Enzyme activity 4.8 U/L. Second mutation not identified. Patient is on biotin supplements. |
15658435 |
Exon 03 |
Missense |
c.326T>G |
p.V109G |
Pathogenic |
unknown |
Muhl (2001) |
|
15658443 |
Exon 03 |
Missense |
c.334G>C |
p.E112Q |
Pathogenic |
yes |
Pomponio (1997a) |
|
15658443 |
Exon 03 |
Missense |
c.334G>A |
p.E112K |
Pathogenic |
yes |
Laszlo (2003) |
|
15658450 |
Exon 03 |
Missense |
c.341G>T |
p.G114V |
Pathogenic |
yes |
Wolf (2005) |
|
15658465 |
Exon 03 |
Missense |
c.356A>G |
p.N119S |
Pathogenic-partial |
unknown |
Procter (2016) |
 Enzyme activity @ 1.1 U/L w/no paired control. Seen with c.1459delT |
15658473 |
Exon 03 |
Missense |
c.364A>G |
p.R122G |
Pathogenic |
unknown |
Norrgard (1999) |
|
15658491 |
Exon 03 |
Missense |
c.382T>G |
p.F128V |
Pathogenic |
unknown |
Swango (1998) |
|
15658502 |
Exon 03 |
Deletion |
c.393del |
p.F131Lfs*28 |
Pathogenic |
yes |
Wolf (2002) |
|
15658508 |
Exon 03 |
Silent |
c.399G>A |
p.P133P |
Benign |
unknown |
Procter (2016) |
 Enzyme activity @ 2.9 U/L. Seen with c.1368A>C,p.Q456H. |
15658515 |
Exon 03 |
Deletion |
c.406delC |
p.Q136fs*23 |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 0.8U/L. Seen with c.1330G>C,p.D444H. |
15658516 |
Exon 03 |
Insertion |
c.407_408insA |
p.Q136fs |
Pathogenic |
unknown |
Onay H et al, unpublished |
 Patient with partial enzyme deficiency. D444H was found as a second mutation. |
15658533 |
Exon 03 |
Missense |
c.424C>A |
p.P142T |
Pathogenic |
yes |
Sarafoglou (2009) |
|
15658537/15683532 |
Exon 03 |
Missense |
c.428G>T |
p.C143F |
Suspected pathogenic |
yes |
Onay H et al, unpublished |
 Variant was seen in trans with T532M. C143F is considered " probably="" damaging"="" by="" polyphen."=" |
15658552 |
Exon 03 |
Missense |
c.443G>A |
p.R148H |
Pathogenic |
unknown |
Ohlsson (2010) |
|
15658553 |
Exon 03 |
Slient |
c.444C>A |
p.A148A |
Benign |
unknown |
Pico and Couce (1999) |
|
15658554 |
Exon 03 |
Missense |
c.445T>C |
p.F149L |
Pathogenic |
unknown |
Norrgard (1999) |
|
15658563 |
Exon 03 |
Missense |
c.454A>C |
p.T152P |
Pathogenic |
unknown |
Milankovics (2007) |
|
15658564 |
Exon 03 |
Missense |
c.455C>G |
p.T152R |
Pathogenic |
no |
Li (2014) |
 Enzyme activity @ 1.8 U/L. Seen with c.1330G>C;p.D444H. |
15658568 |
Exon 04 |
Slice Site |
c.459G>A |
p.E153E |
Pathogenic |
yes |
Pomponio (1997a) |
|
15658569 |
Exon 04 |
Insertion |
c.460-8dupT |
p.V154Cfs*3 |
Benign |
unknown |
Procter (2016) |
 Enzyme activity @ 2.8 U/L with a paired control in the normal range. |
15660833 |
Exon 04 |
Nonsense |
c.466C>T |
p.Q156X |
Pathogenic |
yes |
Pomponio (2000b) |
|
15660836 |
Exon 04 |
Missense |
c.469C>T |
p.R157C |
Pathogenic |
unknown |
Milankovics (2007) |
|
15660837 |
Exon 04 |
Missense |
c.470G>A |
p.R157H |
Pathogenic |
yes |
Pomponio (1997a) |
|
15660837;15661697 |
Exon 04;Exon 04 |
Missense;Missense |
c.470G>A;1330G>C |
p.R157H;D444H |
Pathogenic |
unknown |
Norrgard (1999) |
 These 2 pathogenic variations, p.R157H;D444H, were observed both in haplotype and alone. When observed alone D444H is considered a mild mutation. |
15660852 |
Exon 04 |
Missense |
c.485C>T |
p.A162V |
Pathogenic |
unknown |
Norrgard (1999) |
|
15660857 |
Exon 04 |
Deletion |
c.490_491del |
p.R164Gfs*17 |
Pathogenic |
yes |
Pomponio (2000b) |
|
15660878;15661697 |
Exon 04;Exon 04 |
Missense;Missense |
c.511G>A;1330G>C |
p.A171T;D444H |
Pathogenic |
yes |
Norrgard (1999) |
 These 2 sequence variants, p.A171T;D444H have been observed in haplotype. A171T is never observed alone and causes a severe phenotype in conjunction with D444H. |
15660882 |
Exon 04 |
Missense |
c.515A>G |
p.N172S |
Pathogenic |
unknown |
Muhl (2001) |
|
15660885 |
Exon 04 |
Missense |
c.518T>G |
p.L173R |
Pathogenic |
yes |
Monaghan and Wolf, unpublished |
|
15660895 |
Exon 04 |
Missense |
c.528G>T |
p.K176N |
Pathogenic |
unknown |
Norrgard (1999) |
|
15660896 |
Exon 04 |
Missense |
c.529G>A |
p.E177K |
Pathogenic |
no |
Lara (2015) |
 Enzyme activity @ 2.0 U/L. Seen with c.1595C>T,p.T532M. May be mildly pathogenic. Abnormal NB screen. |
15660911 |
Exon 04 |
Deletion |
c.544del |
p.S182Vfs*82 |
Pathogenic |
yes |
Pomponio (2000b) |
|
15660924 |
Exon 04 |
Missense |
c.557G>A |
p.C186Y |
Pathogenic |
unknown |
Pomponio (2000a) |
|
15660926 |
Exon 04 |
Missense |
c.559C>T |
p.P187S |
Pathogenic |
unknown |
Iqbal (2010) |
|
15660933 |
Exon 04 |
Missense |
c.566A>G |
p.D189G |
Uncertain |
unknown |
Procter (2016) |
 Seen with c.-34C>T. Enzyme activity @ 5.6 U/L |
15660949 |
Exon 04 |
Missense |
c.582C>G |
p.F194L |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.1 U/L. Seen with c.1330G>C,p.D444H. |
15660950 |
Exon 04 |
Missense |
c.583A>G |
p.N195D |
Pathogenic |
yes |
Pomponio (1997a) |
|
15660951 |
Exon 04 |
Missense |
c.584A>G |
p.N195S |
Pathogenic |
unknown |
Milankovics (2007) |
|
15660954 |
Exon 04 |
Missense |
c.587C>G |
p.T196R |
Pathogenic |
yes |
Pomponio (2000a) |
|
15660961 |
Exon 04 |
Deletion |
c.594_596del |
p.V199del |
Pathogenic |
yes |
Pomponio (1997a) |
|
15660961 |
Exon 04 |
Deletion |
c.594del |
p.V199Cfs*65 |
Pathogenic |
unknown |
Funghini (2002) |
|
15660962 |
Exon 04 |
Missense |
c.595G>A |
p.V199M |
Pathogenic |
unknown |
Wolf (2002) |
|
15660972 |
Exon 04 |
Missense |
c.605A>T |
p.N202I |
Pathogenic |
unknown |
Ohlsson (2010) |
|
15660992 |
Exon 04 |
Missense |
c.625C>T |
p.R209C |
Pathogenic-partial |
unknown |
Procter (2016) |
 Enzyme activity @ 2.1 U/L. Seen with c.1368A>C,p.Q456H. |
15660993 |
Exon 04 |
Missense |
c.626G>A |
p.R209H |
Pathogenic |
no |
Li (2014) |
 Enzyme activity @ 0.8 U/L. Seen with c.1368A>C;p.Q456H. |
15660996 |
Exon 04 |
Missense |
c.629A>G |
p.Y210C |
Pathogenic |
yes |
Pomponio (1997a) |
|
15660998 |
Exon 04 |
Missense |
c.631C>T |
p.R211C |
Pathogenic |
unknown |
Norrgard (1999) |
|
15660998 |
Exon 04 |
Deletion |
c.631delC |
p.R211Vfs*53 |
Pathogenic |
yes |
Tiar (2014) |
|
15660998 |
Exon 04 |
Missense |
c.631C>A |
p.R211S |
Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 0.3, 0.6 U/L. Seen with c.1595C>T,p.T532M. Abnormal NB screen. |
15660999 |
Exon 04 |
Missense |
c.632G>A |
p.R211H |
Uncertain |
unknown |
Thodi (2011) |
|
15660999 |
Exon 04 |
Missense |
c.632G>T |
p.R211L |
Likely Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 1.4 U/L. Seen with c.1330G>C,p.D444Hand in cis with c.310-15delT. Abnormal NB screen. |
15661010 |
Exon 04 |
Missense |
c.643C>T |
p.L215F |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661012 |
Exon 04 |
Slient |
c.645C>T |
p.L215L |
Benign |
unknown |
Hymes (2001) |
|
15661013 |
Exon 04 |
Missense |
c.646T>A |
p.Y216N |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.0 U/L. Seen with c.1330G>C;p.D444H. |
15661019 |
Exon 04 |
Missense |
c.652G>C |
p.E218Q |
Pathogenic |
yes |
Laszlo (2003) |
|
15661021 |
Exon 04 |
Missense |
c.654G>C |
p.E218D |
Pathogenic |
unknown |
Wolf (2005) |
|
15661031 |
Exon 04 |
Missense |
c.664G>C |
p.D222H |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.0 U/L w/no paired control. Seen with c.1330G>C,p.D444H. |
15661049 |
Exon 04 |
Missense |
c.682G>T |
p.D228Y |
Pathogenic |
unknown |
Swango (1998) |
|
15661050 |
Exon 04 |
Missense |
c.683A>G |
p.D228G |
Pathogenic |
no |
Li (2014) |
 Enzyme activity @ 2.4 U/L.Seen with c.1330G>C;p.D444H. |
15661059 |
Exon 04 |
Deletion |
c.692delC |
p.F232Lfs*32 |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.4 U/L. Seen with c.1330G>C,p.D444H. |
15661062 |
Exon 04 |
Missense |
c.695T>C |
p.F232S |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.4 U/L. Seen with c.1330G>C,p.D444H. |
15661068 |
Exon 04 |
Missense |
c.701C>T |
p.T234I |
Pathogenic |
no |
Li (2014) |
 Enzyme activities @ 2.3 U/L with c.1330G>C;p.D444H in one patient. Enzyme activity @ 0.8 U/L in a homozygous patient. |
15661076 |
Exon 04 |
Missense |
c.709G>A |
p.A237T |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.6 U/L w/no paired control. Seen with c.1330G |
15661101 |
Exon 04 |
Missense |
c.734G>A |
p.C245Y |
Pathogenic |
yes |
Wolf (2005) |
|
15661110 |
Exon 04 |
Missense |
c.743T>C |
p.I248IT |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ < 0.4 U/L with a paired control in the normal range. Seen with c.528G>T,p.K176N. |
15661122 |
Exon 04 |
Missense |
c.755A>G |
p.D252G |
Pathogenic |
unknown |
Norrgard (1999) |
|
15661124 |
Exon 04 |
Missense |
c.757C>T |
p.P253S |
Pathogenic |
yes |
Wolf (2005) |
|
15661125 |
Exon 04 |
Missense |
c.758C>T |
p.P253L |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 0.1 U/L w/no paired control. Seen with c.1489C>T,p.P497S. |
15661131 |
Exon 04 |
Missense |
c.764T>C |
P.I255T |
Pathogenic |
unknown |
Ohlsson (2010) |
|
15661137 |
Exon 04 |
Missense |
c.770T>A |
p.V257D |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.5 U/L. Seen with c.1330G>C,p.D444H. |
15661150 |
Exon 04 |
Nonsense |
c.783C>G |
p.Y261X |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.3 U/L. Seen with c.1330G>C,p.D444H. |
15661161 |
Exon 04 |
Missense |
c.794A>T |
p.H265L |
Pathogenic |
yes |
Wolf (2002) |
|
15661161;15661300 |
Exon 04 |
Missense;Missense |
c.794A>T;933T>G |
p.H265L;S311R |
Pathogenic |
yes |
Iqbal (2010) |
 These 2 pathogenic variations, p.H265L;S311R, were observed both in haplotype and alone. |
15661181 |
Exon 04 |
Missense |
c.814T>G |
p.W272G |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.6 U/L w/no paired control. Seen with c.1330G>cCp.D444H. |
15661182 |
Exon 04 |
Nonsense |
c.815G>A |
p.W272X |
Uncertain |
unknown |
Procter (2016) |
 Abnormal newborn screen. Sister is carrier of c.1330G>C;p.D444H. Caucasian |
15661199 |
Exon 04 |
Missense |
c.832C>G |
p.L278V |
Pathogenic |
yes |
Laszlo (2003) |
|
15661199 |
Exon 04 |
Missense |
c.832C>A |
p.L278I |
Likely Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 2.0. Seen with c.1330G>C,p.D444H. Abnormal NB screen. |
15661200 |
Exon 04 |
Missense |
c.833T>C |
p.L278P |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661203 |
Exon 04 |
Missense |
c.836T>G |
p.L279W |
Pathogenic |
unknown |
Muhl (2001) |
|
15661203 |
Exon 04 |
Nonsense |
c.836T>A |
p.L279X |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ <0.4 U/L. |
15661209 |
Exon 04 |
Missense |
c.842C>T |
p.A281V |
Pathogenic |
no |
Lara (2015) |
 Enzyme activity @ 1.7 U/L. Seen with c.1330G>C,p.D444H. Abnormal NB screen. |
15661223 |
Exon 04 |
Missense |
c.856A>G |
p.K286E |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity 0.6 U/L. Seen with c.1330G>C,p.D444H. |
15661225 |
Exon 04 |
Deletion |
c.858 delA |
p.K286Kfs*22 |
Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 1.1 U/L. Seen with c.310-15delT. Abnormal NB screen. |
15661232 |
Exon 04 |
Missense |
c.865G>C |
p.A289P |
Pathogenic |
no |
Procter (2016) |
 Enzyme activity 0.6 U/L. Abnormal NB screen |
15661247 |
Exon 04 |
Missense |
c.880A>G |
p.I294V |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 3.3 U/L w/no paired control. Second mutation not identified. |
15661254 |
Exon 04 |
Missense |
c.887T>G |
p.V296G |
Pathogenic |
yes |
Wolf (2002) |
|
15661262 |
Exon 04 |
Missense |
c.895G>C |
p.A299P |
Pathogenic |
unknown |
Procter (2016) |
 Seen with c.1413T>C; synonymous. |
15661263 |
Exon 04 |
Missense |
c.896C>T |
p.A299V |
Pathogenic |
unknown |
Pico and Couce (1999) |
|
15661265 |
Exon 04 |
Missense |
c.898A>C |
p.N300H |
Pathogenic |
no |
Li (2014) |
 Enzyme activity @ 1.9 U/L. Seen with c.1330G>C;p.D444H. |
15661296 |
Exon 04 |
Missense |
c.929G>A |
p.G310E |
Pathogenic |
unknown |
Pomponio (2000a) |
|
15661299 |
Exon 04 |
Missense |
c.932G>A |
p.S311N |
Pathogenic |
unknown |
Norrgard (1999) |
|
15661299 |
Exon 04 |
Missense |
c.932G>C |
p.S311T |
Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 1.8 U/L. Seen with c.1314T>A;p.Y438X. May be mildly pathogenic. Abnormal NB screen. |
15661300 |
Exon 04 |
Deletion |
c.933delT |
p.S311Rfs*23 |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661300 |
Exon 04 |
Missense |
c.933T>G |
p.S311R |
Pathogenic |
yes |
Iqbal (2010) |
 Observed as homozygous. |
15661301 |
Exon 04 |
Missense |
c.934G>A |
p.G312S |
Pathogenic |
yes |
Wolf (2002) |
|
15661302 |
Exon 04 |
Missense |
c.935G>A |
p.G312D |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661335 |
Exon 04 |
Missense |
c.968A>G |
p.H323R |
Pathogenic |
unknown |
Swango (1998) |
|
15661368 |
Exon 04 |
Missense |
c.1001T>A |
p.I334N |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.2 U/L w/no paired control. Seen with c.1330G>C,p.D444H. |
15661413 |
Exon 04 |
Missense |
c.1046A>C |
p.N349T |
Uncertain |
unknown |
Procter (2016) |
 Enzyme activity @ 1.9 U/L. Seen with c.1330G>C,p.D444H. |
15661416 |
Exon 04 |
Deletion |
c.1049del |
p.A350fs |
Pathogenic |
yes |
Wolf (2002) |
|
15661419 |
Exon 04 |
Deletion |
c.1052del |
p.T351fs |
Pathogenic |
yes |
Wolf (2002) |
|
15661457 |
Exon 04 |
Missense |
c.1081T>G |
p.F361V |
Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 1.0, 1.6 and 1.3, 2.1 U/L. Observed as homozygous in two unrelated patients (1.0 and 1.6); co-inherited with p.H485Q (1.3) and co-inherited with p.D444H (2.1) in another two patients. Abnormal NB screen. |
15661463 |
Exon 04 |
Missense |
c.1096T>C |
p.S366P |
Pathogenic |
yes |
Wolf (1998) |
|
15661463 |
Exon 04 |
Duplication |
c.1096-1097dupTC |
p.G367Qfs*23 |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 0.9 U/L. Seen with c.1330G>C,p.D444H. |
15661473 |
Exon 04 |
Missense |
c.1106C>T |
p.P369L |
Pathogenic |
yes |
Wolf (2002) |
|
15661493 |
Exon 04 |
Nonsense |
c.1126C>T |
p.Q376X |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ <0.4 U/L. Seen with c.1612C>T,p.R538C. |
15661524 |
Exon 04 |
Nonsense |
c.1157G>A |
p.W386X |
Pathogenic |
unknown |
Wolf (2005) |
|
15661525 |
Exon 04 |
Nonsense |
c.1158G>A |
p.W386X |
Pathogenic |
unknown |
Norrgard (1999) |
|
15661538 |
Exon 04 |
Missense |
c.1171C>T |
p.P391S |
Benign |
unknown |
Hymes (2001) |
|
15661538;15661701 |
Exon 04;Exon 04 |
Missense;Missense |
c.1171C>T;1334G>T |
p.P391S;G445V |
Pathogenic |
yes |
Wolf (2005) |
 These 2 pathogenic variations, p.P391S;G445V were observed both in haplotype and alone. |
15661558 |
Exon 04 |
Deletion |
c.1191_1192del |
p.E397Dfs*4 |
Pathogenic |
unknown |
Wolf (2002) |
|
15661572 |
Exon 04 |
Missense |
c.1205A>G |
p.N402S |
Pathogenic |
unknown |
Ohlsson (2010) |
|
15661574 |
Exon 04 |
Missense |
c.1207T>G |
p.F403V |
Pathogenic |
unknown |
Norrgard (1999) |
 Observed in a patient with c.1330G>C. When observed alone D444H is considered a mild mutation. |
15661578 |
Exon 04 |
Missense |
c.1211C>T |
p.T404I |
Pathogenic |
yes |
Funghini (2002) |
|
15661581 |
Exon 04 |
Missense |
c.1214T>C |
p.L405P |
Pathogenic |
unknown |
Ohlsson (2010) |
|
15661594 |
Exon 04 |
Indel |
c.1227_1241delins11 |
p.W409fs |
Pathogenic |
unknown |
Norrgard (1999) |
|
15661604 |
Exon 04 |
Missense |
c.1237G>A |
p.G413S |
Pathogenic |
yes |
Monaghan and Wolf, unpublished |
|
15661606 |
Exon 04 |
Deletion |
c.1239del |
p.G413fs |
Pathogenic |
unknown |
Wolf (2002) |
|
15661608 |
Exon 04 |
Deletion |
c.1241_1252del |
p.Y414_V417del |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 0.5 U/L. Seen with c.1330G>C,p.D444H. |
15661616 |
Exon 04 |
Missense |
c.1249G>T |
p.V417F |
Pathogenic |
unknown |
Sarafoglou (2009) |
|
15661619 |
Exon 04 |
Missense |
c.1252T>C |
p.C418R |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.9 U/L w/no paired control. Seen with c.13330G>C,p.D444H-het and c.1413T>C,p.C471C. |
15661620 |
Exon 04 |
Missense |
c.1253G>C |
p.C418S |
Pathogenic |
yes |
Laszlo (2003) |
|
15661631 |
Exon 04 |
Duplication |
c.1264dup |
p.G421fs |
Pathogenic |
yes |
Iqbal (2010) |
|
15661634 |
Exon 04 |
Missense |
c.1267T>C |
p.C423R |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661635 |
Exon 04 |
Missense |
c.1268G>C |
p.C423W |
Pathogenic |
unknown |
Muhl (2001) |
|
15661638 |
Exon 04 |
Missense |
c.1271G>A |
p.C424Y |
Pathogenic |
unknown |
Wolf (2005) |
|
15661638 |
Exon 04 |
Missense |
c.1271G>C |
p.C424S |
Pathogenic |
unknown |
Wolf (2005) |
|
15661642 |
Exon 04 |
Nonsense |
c.1275T>G |
p.Y425X |
Pathogenic |
unknown |
Iqbal (2010) |
|
15661649 |
Exon 04 |
Missense |
c.1282T>A |
p.Y428N |
Likely Pathogenic |
unknown |
Bridget Rogers, unpublished - 2015 -email dec030, 2011 |
 Enzyme activity @ <1.0 nmol/mL/min. Seen with c.1368A>C,p.Q456H |
15661651 |
Exon 04 |
Nonsense |
c.1284C>A |
p.Y428X |
Pathogenic |
yes |
Wang (2009) |
|
15661651 |
Exon 04 |
Silent |
c.1284C>T |
p.Y428Y |
Benign |
unknown |
Wolf (2005) |
 One benign variant, p.Y428Y was observed together with one pathogenic variant, p.P497S. The latter variant is also observed alone. |
15661676 |
Exon 04 |
Missense |
c.1309C>G |
p.L437V |
Pathogenic-partial |
unknown |
Procter (2016) |
 Enzyme activity @ 3.3 U/L with abnormal cutoff at 4.5 U/L @ another lab. Seen with c.1330G>C,p.D444H. Abnormal newborn screen with reduced BTD activity. Caucasian. |
15661680 |
Exon 04 |
Missense |
c.1313A>G |
p.Y438C |
Pathogenic |
yes |
Wolf (2002) |
|
15661681 |
Exon 04 |
Nonsense |
c.1314T>A |
p.Y438X |
Pathogenic |
unknown |
Neto (2004) |
|
15661695 |
Exon 04 |
Missense |
c.1328T>C |
p.F443S |
Suspected pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @<0.4 U/L with a paired control in the normal range. Second mutation not identified. Hispanic. |
15661697 |
Exon 04 |
Missense |
c.1330G>C |
p.D444H |
Pathogenic |
yes |
Swango (1998) |
|
15661700 |
Exon 04 |
Missense |
c.1333G>A |
p.G445R |
Pathogenic |
unknown |
Ohlsson (2010) |
|
15661701 |
Exon 04 |
Missense |
c.1334G>T |
p.G445V |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661701 |
Exon 04 |
Missense |
c.1334G>A |
p.G445E |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.3 U/L. Seen with c.1330G>C,p.D444H. |
15661706 |
Exon 04 |
Missense |
c.1339C>T |
p.H447Y |
Pathogenic |
yes |
Chedrawi AK (2008) |
|
15661719 |
Exon 04 |
Missense |
c.1352G>A |
p.G451D |
Pathogenic |
unknown |
Swango (1998) |
 Associated with partial biotinidase deficiency |
15661719 |
Exon 04 |
Deletion |
c.1352_1353delGC |
p.G451Dfs*32 |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.4 U/L. Seen with c.1330G>C,p.D444H. |
15661728 |
Exon 04 |
Missense |
c.1361A>G |
p.Y454C |
Pathogenic |
unknown |
Wolf (2005) |
 Seen in haplotype with c.235C>T |
15661735 |
Exon 04 |
Missense |
c.1368A>C |
p.Q456H |
Pathogenic |
yes |
Norrgard (1999) |
|
15661736 |
Exon 04 |
Missense |
c.1369G>A |
p.V457M |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661739 |
Exon 04 |
Insertion |
c.1372_1373insT |
p.C458Lfs*26 |
Pathogenic |
no |
Li (2014) |
 Enzyme activity @ 2.0 U/L. Seen with c.968A>G;p.H323R. |
15661751 |
Exon 04 |
Deletion |
c.1384del |
p.R462Gfs*39 |
Pathogenic |
yes |
Wang (2009) |
|
15661755 |
Exon 04 |
Missense |
c.1388G>A |
p.C463Y |
Pathogenic |
yes |
Wolf (2002) |
|
15661761 |
Exon 04 |
Indel |
c.1394dupG |
p.L466fs |
Pathogenic |
yes |
Couce (2011) |
|
15661780 |
Exon 04 |
Slient |
c.1413T>C |
p.C471C |
Benign |
no |
Pomponio (1998) |
|
15661799 |
Exon 04 |
Missense |
c.1432G>C |
p.A478P |
Pathogenic |
unknown |
Sarafoglou (2009) |
|
15661799 |
Exon 04 |
Missense |
c.1432G>A |
p.A478T |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.4 U/L with a paired control in the normal range. Seen with c.755A>G,p.D252G. |
15661822 |
Exon 04 |
Missense |
c.1455C>G |
p.H485Q |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 0.7 U/L. Seen with a complex mutation [c.1330G>C,c.511G>A; p.D444H,p.A171T] |
15661825 |
Exon 04 |
Deletion |
c.1458delG |
p.W487Gfs*14 |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 0.2 U/L. Seen with c.278A>G,p.Y93C. |
15661826 |
Exon 04 |
Missense |
c.1459T>C |
p.W487R |
Pathogenic |
yes |
Pomponio (2000b) |
|
15661826 |
Exon 04 |
Deletion |
c.1459delT |
p.W487Gfs*14 |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 3.3 U/L w/no paired control. Seen with c.356A>G,p.N119S. |
15661830 |
Exon 04 |
Missense |
c.1463G>A |
p.G488D |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661833 |
Exon 04 |
Missense |
c.1466A>C |
p.N489T |
Pathogenic |
no |
Pomponio (1998) |
|
15661848 |
Exon 04 |
Missense |
c.1481A>G |
p.Y494C |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.3 U/L. |
15661856 |
Exon 04 |
Missense |
c.1489C>T |
p.P497S |
Pathogenic |
yes |
Norrgard (1999) |
|
15661860 |
Exon 04 |
Duplication |
c.1493dup |
p.P498Ffs*13 |
Pathogenic |
yes |
Wang (2009) |
|
15661878 |
Exon 04 |
Missense |
c.1511T>A |
p.M504K |
Pathogenic |
unknown |
Laszlo (2003) |
|
15661893 |
Exon 04 |
Missense |
c.1526C>G |
p.P509R |
Pathogenic |
unknown |
Procter (2016) |
|
15661898 |
Exon 04 |
Missense |
c.1531C>G |
p.Q511E |
Pathogenic |
yes |
Wolf (2005) |
|
15661924 |
Exon 04 |
Missense |
c.1557T>G |
p.Y519X |
Pathogenic |
yes |
Tiar (2014) |
|
15661962 |
Exon 04 |
Missense |
c.1595C>T |
p.T532M |
Pathogenic |
yes |
Norrgard (1999) |
|
15661977 |
Exon 04 |
Missense |
c.1610G>A |
p.G537V |
Pathogenic |
yes |
Wolf (2002) |
|
15661979 |
Exon 04 |
Missense |
c.1612C>A |
p.R538S |
Uncertain |
unknown |
Procter (2016) |
 Seen multiple times, most often with c.13330G>C,p.D444H. Enzyme activities range from <0.4 U/L to 2.2 U/L. |
15661979 |
Exon 04 |
Missense |
c.1612C>T |
p.R538C |
Pathogenic |
yes |
Pomponio (1997a) |
|
15661980 |
Exon 04 |
Missense |
c.1613G>A |
p.R538H |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 1.5 U/L. Seen with c.1062G>A,p.T354T (polymorphism). |
15661983 |
Exon 04 |
Duplication |
c.1616dup |
p.L539Ffs*3 |
Pathogenic |
unknown |
Norrgard (1999) |
|
15661986 |
Exon 04 |
Missense |
c.1619A>G |
p.Y540C |
Pathogenic |
unknown |
Norrgard (1999) |
|
15661994 |
Exon 04 |
Missense |
c.1627G>C |
p.D543H |
Pathogenic |
unknown |
Muhl (2001) |
|
15661995 |
Exon 04 |
Missense |
c.1628A>T |
p.D543V |
Pathogenic-partial |
unknown |
Procter (2016) |
 Enzyme activity @ 1.9 U/L. Seen with c.310-15delT. |
15661996 |
Exon 04 |
Missense |
c.1629C>A |
p.D543E |
Pathogenic |
unknown |
Procter (2016) |
 Enzyme activity @ 2.4 U/L with paired control in normal range. Seen with c.1330G>C,p.D444H. |
15678473 |
Exon 04 |
Missense |
c.1601C>T |
p.A534V |
Pathogenic |
no |
Carvalho (2019) |
 Enzyme activity @ 0.3 and 1.8, 2.1 U/L. Observed as homozygous; two enzimatic dosages at different times with the same result (0.3/0.3). Co-inherited with p.D444H in two other patients (1.8/2.1). Abnormal NB screen. |