BTD Database

• Reference sequences were NC_000003.10 and NM_000060.2. cDNA number 1 is the "A" of the start codon.
• Frameshift is documented by the original amino acid followed by the codon number and "fs" (ex. Leu159 fs).
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• "Live Search" any term in the search box, such as "exon" , "missense", "benign" , etc...
• Due to instability of the biotinidase enzyme, ARUP and other laboratories require samples submitted for biotinidase activity testing be accompanied by a paired control drawn at the same time as the patient. This paired control should be collected from a normal, healthy individual who is not biologically related to the patient. ARUP's normal reference range for this assay is 3.5-13.8 U/L.

221 variants found

Genomic Position	Location ▾	Mutation Type	Nucleotide Change	Protein Change	Classification	Symptomatic Patient	References	Comments
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T		Benign	unknown	Procter et al, unpublished	Seen with c.566A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.