TH (Tyrosine 3-monooxygenase) variants and mutations
TH (also known as Tyrosine 3-monooxygenase) is a human protein-coding gene encoding a tyrosine 3-monooxygenase protein. It catalyzes the rate-limiting conversion of tyrosine to L-DOPA before dopamine, norepinephrine, and epinephrine synthesis. Biallelic pathogenic variants cause tyrosine-hydroxylase deficiency, ranging from dopa-responsive dystonia to severe infantile parkinsonism. This analysis covers 465 TH variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes Autosomal recessive dopa-responsive dystonia, TH-deficient dopa-responsive dystonia, and dopa-responsive dystonia. Example TH variants include M1?, M1T, and P4L.
Variant analysis overview
- Gene: TH
- Protein: Tyrosine 3-monooxygenase
- UniProt accession: P07101
- Organism: Homo sapiens
- Variants analyzed: 465
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 183 unspecified-consequence records; 4 stop lost; 60 synonymous variants; 182 missense variants; 11 frameshift variants; 10 stop-gained variants; 1 protein altering variant; 2 in-frame insertions; 2 splice-region variants; 3 in-frame deletions; 6 substitution
- Prediction scores: 362 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Autosomal recessive dopa-responsive dystonia, TH-deficient dopa-responsive dystonia, dopa-responsive dystonia, tyrosine hydroxylase deficiency, dystonia 5, pheochromocytoma, adrenal gland pheochromocytoma, Intellectual disability, Dystonia, dystonic disorder, hereditary disease, type 2 diabetes mellitus.
Protein structure and variant hotspots
- Protein features: 3 binding sites; 4 post-translational modification sites.
- PTM context: 1 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable TH variants
Examples include M1?, M1T, P4L, D5T, F14L, R16G, S19C, E20Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- M1T (p.Met1Thr), rs201932766, ClinGen CA5818897, ClinVar RCV000672231, MetaLR 0.98, MetaSVM 1.05, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P4L (p.Pro4Leu), rs2495843389, ClinGen CA379112908, ClinVar RCV003028930, NCI-TCGA Cosmic COSV6076, REVEL 0.51, MetaLR 0.97, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- D5T (p.Asp5Thr), NCI-TCGA Cosmic COSV6076, Variant assessed as somatic; high impact.
- F14L (p.Phe14Leu), rs2495842917, ClinGen CA379112850, ClinVar RCV002620306, REVEL 0.57, MetaLR 0.93, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- R16G (p.Arg16Gly), rs753005879, ClinGen CA379112846, ClinVar RCV002730799, AlphaMissense 0.64, MetaLR 0.98, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- S19C (p.Ser19Cys), rs766704202, ClinGen CA5818875, cosmic curated COSV60766, ClinVar RCV002295375, REVEL 0.62, MetaLR 0.98, Conflicting interpretations, not specified; Autosomal recessive DOPA responsive dystonia
- E20Q (p.Glu20Gln), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60767, Variant assessed as somatic; moderate impact.
- A28P (p.Ala28Pro), rs769342435, ClinGen CA379112772, ClinVar RCV002828196, AlphaMissense 0.18, MetaLR 0.96, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- R32* (p.Arg32Ter), rs1554924328, ClinGen CA658821342, ClinVar RCV000672473, Uncertain significance
- A36T (p.Ala36Thr), rs376736869, ClinGen CA5818831, ClinVar RCV001200079, ClinVar RCV001277937, AlphaMissense 0.07, MetaLR 0.87, Conflicting interpretations, Inborn genetic diseases; not provided; Autosomal recessive DOPA responsive dysto
- P37L (p.Pro37Leu), rs775961364, ClinGen CA5818829, ClinVar RCV000664631, ClinVar RCV002530633, AlphaMissense 0.08, MetaLR 0.92, Uncertain significance, Inborn genetic diseases; Autosomal recessive DOPA responsive dystonia
- P37S (p.Pro37Ser), rs2495836730, ClinGen CA379112707, ClinVar RCV003032746, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P39L (p.Pro39Leu), rs2495836664, ClinGen CA379112695, ClinVar RCV002588612, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- L41I (p.Leu41Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G43S (p.Gly43Ser), rs200295434, ClinGen CA5818825, ClinVar RCV003050946, AlphaMissense 0.09, MetaLR 0.86, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- S44F (p.Ser44Phe), rs1313952475, ClinGen CA379112664, ClinVar RCV000671704, AlphaMissense 0.10, MetaLR 0.88, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P45L (p.Pro45Leu), rs148235227, ClinGen CA5818822, ClinVar RCV001195971, ClinVar RCV002547110, AlphaMissense 0.09, MetaLR 0.87, Conflicting interpretations, Inborn genetic diseases; Autosomal recessive DOPA responsive dystonia
- G48* (p.Gly48Ter), rs2495836407, ClinGen CA379112642, ClinVar RCV003474109, Likely pathogenic
- T49N (p.Thr49Asn), rs540910436, ClinGen CA5818819, ClinVar RCV002914708, AlphaMissense 0.10, MetaLR 0.88, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- A50V (p.Ala50Val), rs756331878, ClinGen CA5818818, ClinVar RCV000552368, ClinVar RCV004669026, CADD 2.61, SIFT 0.30, Uncertain significance, Inborn genetic diseases; Autosomal recessive DOPA responsive dystonia
- A51T (p.Ala51Thr), rs1186732715, ClinGen CA379112628, ClinVar RCV001971378, AlphaMissense 0.08, MetaLR 0.89, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P52L (p.Pro52Leu), rs781594548, ClinGen CA5818816, ClinVar RCV003061460, AlphaMissense 0.11, MetaLR 0.91, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- S55F (p.Ser55Phe), rs1195830888, ClinGen CA379112602, ClinVar RCV000671574, AlphaMissense 0.13, MetaLR 0.89, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P60Q (p.Pro60Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R61S (p.Arg61Ser), rs1330998143, ClinGen CA379112566, ClinVar RCV001302461, AlphaMissense 0.15, MetaLR 0.87, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P63S (p.Pro63Ser), rs1353124114, NCI-TCGA Cosmic COSV6076, cosmic curated COSV60767, AlphaMissense 0.16, MetaLR 0.96, Variant assessed as somatic; moderate impact.
- P63T (p.Pro63Thr), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60766, Variant assessed as somatic; moderate impact.
- R64L (p.Arg64Leu), NCI-TCGA Cosmic COSV6076, Variant assessed as somatic; moderate impact.
- G67V (p.Gly67Val), rs1358506695, ClinGen CA379112524, ClinVar RCV002716979, AlphaMissense 0.61, MetaLR 0.97, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- K78N (p.Lys78Asn), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60766, Variant assessed as somatic; moderate impact.
- A83T (p.Ala83Thr), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60768, Variant assessed as somatic; moderate impact.
- A87E (p.Ala87Glu), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10014, Variant assessed as somatic; moderate impact.
- A90T (p.Ala90Thr), NCI-TCGA TCGA novel, REVEL 0.31, CADD 9.13, Variant assessed as somatic; moderate impact.
- A101A (p.Ala101Ala), rs7950050, Benign
- A103T (p.Ala103Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E106K (p.Glu106Lys), rs1424936497, NCI-TCGA Cosmic COSV6076, cosmic curated COSV60766, gnomAD rs1424936497, AlphaMissense 0.20, MetaLR 0.87, Variant assessed as somatic; moderate impact.
- E108K (p.Glu108Lys), rs1038830878, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10014, gnomAD rs1038830878, AlphaMissense 0.13, MetaLR 0.81, Variant assessed as somatic; moderate impact.
- A111T (p.Ala111Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V112M (p.Val112Met), rs6356, ClinGen CA342583, cosmic curated COSV60767, ClinVar RCV000021078, AlphaMissense 0.08, MetaLR 0.79, Benign/Likely benign, not specified; not provided; Schizophrenia
- R120M (p.Arg120Met), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60767, Variant assessed as somatic; moderate impact.
- K132N (p.Lys132Asn), NCI-TCGA Cosmic COSV1001, Variant assessed as somatic; moderate impact.
- F134S (p.Phe134Ser), rs2495828134, ClinGen CA379112128, ClinVar RCV003140996, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- R151K (p.Arg151Lys), rs2495821858, ClinGen CA379129249, ClinVar RCV002705690, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P152L (p.Pro152Leu), rs760017478, ClinGen CA5818695, NCI-TCGA Cosmic COSV6076, cosmic curated COSV60766, AlphaMissense 0.09, MetaLR 0.90, Conflicting interpretations, Autosomal recessive DOPA responsive dystonia; Inborn genetic diseases; not provi
- R153* (p.Arg153Ter), rs771610752, ClinGen CA5818693, cosmic curated COSV10605, ClinVar RCV000521520, Pathogenic
- R153Q (p.Arg153Gln), rs201093528, ClinGen CA5818692, cosmic curated COSV60768, ClinVar RCV001273884, AlphaMissense 0.08, MetaLR 0.90, Conflicting interpretations, Inborn genetic diseases; Autosomal recessive DOPA responsive dystonia
- R164H (p.Arg164His), rs376881948, ClinGen CA5818680, cosmic curated COSV10014, ClinVar RCV000401042, AlphaMissense 0.19, MetaLR 0.93, Uncertain significance, not provided; Autosomal recessive DOPA responsive dystonia
- R168H (p.Arg168His), rs768153273, ExAC rs768153273, TOPMed rs768153273, gnomAD rs768153273, AlphaMissense 0.08, MetaLR 0.65, Variant assessed as somatic; moderate impact.
- R169G (p.Arg169Gly), rs775175165, ClinGen CA379129024, ClinVar RCV004474677, Uncertain significance, Inborn genetic diseases
- A174S (p.Ala174Ser), NCI-TCGA Cosmic COSV6076, 1000Genomes rs201911992, ExAC rs201911992, TOPMed rs201911992, Uncertain significance
- L176F (p.Leu176Phe), rs1180123781, NCI-TCGA Cosmic COSV6076, cosmic curated COSV60766, gnomAD rs1180123781, AlphaMissense 0.15, MetaLR 0.93, Variant assessed as somatic; moderate impact.
- R180L (p.Arg180Leu), rs1357867110, ClinGen CA379128891, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10014, AlphaMissense 0.11, MetaLR 0.91, Uncertain significance, not provided
- Q181X, rs779228923, []
- E184G (p.Glu184Gly), rs777823354, Uncertain significance
- V186G (p.Val186Gly), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10014, Variant assessed as somatic; moderate impact.
- R187C (p.Arg187Cys), rs762552586, ClinGen CA5818655, ClinVar RCV003326802, ClinVar RCV005103909, AlphaMissense 0.12, MetaLR 0.95, Uncertain significance, Autosomal recessive DOPA responsive dystonia; not provided
- P189S (p.Pro189Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P189T (p.Pro189Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A190S (p.Ala190Ser), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60767, Variant assessed as somatic; moderate impact.
- G191R (p.Gly191Arg), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60768, Variant assessed as somatic; moderate impact.
- G191W (p.Gly191Trp), NCI-TCGA Cosmic COSV6076, Variant assessed as somatic; moderate impact.
- V194=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- W196* (p.Trp196Ter), rs2495817973, ClinGen CA379128675, ClinVar RCV003623967, Pathogenic
- F197L (p.Phe197Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P198S (p.Pro198Ser), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60767, Variant assessed as somatic; moderate impact.
- R199K (p.Arg199Lys), rs2495817893, ClinGen CA379128630, ClinVar RCV003623929, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- S202* (p.Ser202Ter), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10014, Variant assessed as somatic; high impact.
- D205H (p.Asp205His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K206* (p.Lys206Ter), rs2495817747, ClinGen CA379128544, ClinVar RCV002309020, Likely pathogenic
- C207Y (p.Cys207Tyr), UniProt VAR 072863, Pathogenic, in ARSEGS
- D215H (p.Asp215His), rs139807727, ClinGen CA379128454, ClinVar RCV002595191, AlphaMissense 0.75, MetaLR 0.95, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P216A (p.Pro216Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D219Y (p.Asp219Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P223Q (p.Pro223Gln), rs760346235, NCI-TCGA Cosmic COSV6076, cosmic curated COSV60768, ExAC rs760346235, AlphaMissense 0.96, MetaLR 0.99, Uncertain significance
- G224V (p.Gly224Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S226L (p.Ser226Leu), rs372409517, ClinGen CA5818585, cosmic curated COSV60766, ClinVar RCV001271316, AlphaMissense 0.14, MetaLR 0.97, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- S226A (p.Ser226Ala), rs781468666, []
- D227G (p.Asp227Gly), rs1846145669, UniProt VAR 072864, gnomAD rs1846145669, AlphaMissense 0.99, MetaLR 0.99, Pathogenic, in ARSEGS
- Q228* (p.Gln228Ter), rs2495815951, ClinVar RCV004573740, Likely pathogenic
- Q228K (p.Gln228Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R233C (p.Arg233Cys), rs1021029193, ClinGen CA379128112, NCI-TCGA Cosmic COSV6076, cosmic curated COSV60767, AlphaMissense 0.96, MetaLR 0.99, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- R233H (p.Arg233His), rs80338892, ClinGen CA341192, cosmic curated COSV60768, NCI-TCGA Cosmic COSV6076, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, not provided; Autosomal recessive DOPA responsive dystonia
- L236P (p.Leu236Pro), rs121917763, ClinGen CA341191, ClinVar RCV000013118, ClinVar RCV002274896, AlphaMissense 0.85, MetaLR 0.91, Pathogenic/Likely pathogenic, not provided; Autosomal recessive DOPA responsive dystonia
- I237T (p.Ile237Thr), rs2495815684, ClinGen CA379128057, ClinVar RCV003140995, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- A241T (p.Ala241Thr), rs1260455415, ClinGen CA379128007, ClinVar RCV001948824, ClinVar RCV003355679, AlphaMissense 0.31, MetaLR 0.40, Pathogenic/Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- F242L (p.Phe242Leu), rs762932662, ClinGen CA379127979, ClinVar RCV002815845, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- Q243* (p.Gln243Ter), rs2495815488, ClinGen CA379127972, ClinVar RCV002309434, Likely pathogenic
- H246=, rs768037080, NCI-TCGA Cosmic COSV6076, AlphaMissense 0.11, MetaLR 0.91, Uncertain significance, in ARSEGS
- H246Y (p.His246Tyr), UniProt VAR 072866, REVEL 0.73, CADD 23.50, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- G247S (p.Gly247Ser), rs762304556, ClinGen CA5818546, ClinVar RCV001220234, ClinVar RCV001353113, AlphaMissense 0.56, MetaLR 0.60, Pathogenic/Likely pathogenic, not provided; Autosomal recessive DOPA responsive dystonia; Dystonia 5
- P249S (p.Pro249Ser), rs2495812183, ClinGen CA379127500, ClinVar RCV003055520, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- P251L (p.Pro251Leu), rs1846131487, UniProt VAR 071715, Ensembl rs1846131487, AlphaMissense 0.52, MetaLR 0.99, Pathogenic, in ARSEGS
- P251S (p.Pro251Ser), cosmic curated COSV10519, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in ARSEGS
- R252H (p.Arg252His), rs150559011, ClinGen CA5818543, cosmic curated COSV10645, ClinVar RCV001965919, AlphaMissense 0.07, MetaLR 0.93, Likely benign, Autosomal recessive DOPA responsive dystonia
- A257D (p.Ala257Asp), rs1334929754, gnomAD rs1334929754, AlphaMissense 0.10, MetaLR 0.92, Variant assessed as somatic; moderate impact.
- E259G (p.Glu259Gly), UniProt VAR 072868, REVEL 0.83, CADD 31.00, Pathogenic, in ARSEGS
- T262I (p.Thr262Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E265G (p.Glu265Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T269M (p.Thr269Met), rs757607038, ClinGen CA5818512, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10014, AlphaMissense 0.10, MetaLR 0.98, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- G272D (p.Gly272Asp), rs2495806667, ClinGen CA379127051, ClinVar RCV003625853, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- G272S (p.Gly272Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T276P (p.Thr276Pro), rs28934581, ClinGen CA278132, ClinVar RCV000013122, ClinVar RCV005055512, AlphaMissense 0.20, MetaLR 0.98, Uncertain significance, not specified; Autosomal recessive DOPA responsive dystonia
- C279F (p.Cys279Phe), rs1273610334, UniProt VAR 071716, gnomAD rs1273610334, AlphaMissense 0.97, MetaLR 0.99, Pathogenic, in ARSEGS
- G280R (p.Gly280Arg), rs749133549, ExAC rs749133549, TOPMed rs749133549, gnomAD rs749133549, AlphaMissense 0.10, MetaLR 0.95, Variant assessed as somatic; moderate impact.
- G280W (p.Gly280Trp), rs749133549, ExAC rs749133549, TOPMed rs749133549, gnomAD rs749133549, AlphaMissense 0.10, MetaLR 0.95, Variant assessed as somatic; moderate impact.
- F286L (p.Phe286Leu), rs745783108, ClinGen CA379126837, ClinVar RCV003625150, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- A287D (p.Ala287Asp), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60768, Variant assessed as somatic; moderate impact.
- G294R (p.Gly294Arg), rs755536257, ClinGen CA5818489, ClinVar RCV000666139, ClinVar RCV001756124, AlphaMissense 0.11, MetaLR 0.98, Conflicting interpretations, not provided; Autosomal recessive DOPA responsive dystonia
- Y295* (p.Tyr295Ter), rs200730608, ClinGen CA379126704, ClinVar RCV002309950, Likely pathogenic
- R296Q (p.Arg296Gln), rs199961079, ClinGen CA5818486, ClinVar RCV001277075, UniProt VAR 071717, AlphaMissense 0.07, MetaLR 0.94, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- E297K (p.Glu297Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I300V (p.Ile300Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P301A (p.Pro301Ala), UniProt VAR 072870, Pathogenic, in ARSEGS
- Q302* (p.Gln302Ter), rs2495805308, ClinGen CA379126612, ClinVar RCV002306620, Likely pathogenic
- E304D (p.Glu304Asp), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60768, Variant assessed as somatic; moderate impact.
- D305G (p.Asp305Gly), rs2495805221, ClinGen CA379126558, ClinVar RCV003988945, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- S307Y (p.Ser307Tyr), rs2495805112, ClinGen CA379126540, ClinVar RCV002685854, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- F309S (p.Phe309Ser), UniProt VAR 072871, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- T314M (p.Thr314Met), rs121917764, ClinGen CA379126409, ClinVar RCV000623066, UniProt VAR 014029, AlphaMissense 0.94, MetaLR 0.99, Conflicting interpretations, Autosomal recessive DOPA responsive dystonia
- G315D (p.Gly315Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in ARSEGS
- G315S (p.Gly315Ser), rs1288483479, ClinGen CA379126405, ClinVar RCV000674870, UniProt VAR 071718, AlphaMissense 0.53, MetaLR 1.00, Pathogenic/Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- R319P (p.Arg319Pro), UniProt VAR 072872, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- R328W (p.Arg328Trp), rs1428589694, ClinGen CA379126279, ClinVar RCV003058271, ClinVar RCV005869991, AlphaMissense 0.96, MetaLR 0.99, Pathogenic/Likely pathogenic, not provided; Autosomal recessive DOPA responsive dystonia
- L331M (p.Leu331Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A332S (p.Ala332Ser), rs779139610, ClinGen CA379126253, ClinVar RCV003020732, AlphaMissense 0.31, MetaLR 0.98, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- A335T (p.Ala335Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R337H (p.Arg337His), rs28934580, ClinGen CA278131, ClinVar RCV000013121, UniProt VAR 014030, AlphaMissense 0.98, MetaLR 0.99, Pathogenic/Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- V338A (p.Val338Ala), rs2495803118, ClinGen CA379126214, ClinVar RCV003338180, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- Q340* (p.Gln340Ter), rs2495803078, ClinGen CA379126202, ClinVar RCV003624328, Pathogenic
- Y344S (p.Tyr344Ser), rs2495802899, ClinGen CA379126171, ClinVar RCV004474674, Uncertain significance, Inborn genetic diseases
- Y344* (p.Tyr344Ter), gnomAD 11-2165758-G-T, CADD 47.00
- Y370del (p.Tyr370del), gnomAD 11-2165758-GTAC-G, CADD 18.70
- Y344Y (p.Tyr344Tyr), rs1199440700, gnomAD 11-2165758-G-A, CADD 7.17
- S350* (p.Ser350Ter), rs2495802684, ClinVar RCV004573739, Likely pathogenic
- C359F (p.Cys359Phe), rs121917765, ClinGen CA278134, ClinVar RCV000013127, UniProt VAR 072874, AlphaMissense 0.91, MetaLR 0.97, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- C360Y (p.Cys360Tyr), rs529606014, gnomAD 11-2165732-C-T, REVEL 0.91, CADD 24.80
- C360R (p.Cys360Arg), gnomAD 11-2165733-A-G, REVEL 0.94, CADD 26.00
- E362Q (p.Glu362Gln), NCI-TCGA Cosmic COSV6076, cosmic curated COSV60767, REVEL 0.56, CADD 23.50, Variant assessed as somatic; moderate impact.
- E362* (p.Glu362Ter), rs1319079761, gnomAD 11-2165745-C-A, CADD 50.00
- L363P (p.Leu363Pro), rs777379609, Likely pathogenic
- V367V (p.Val367Val), rs1846071177, gnomAD 11-2165713-C-T, CADD 8.16
- V367A (p.Val367Ala), rs573129039, gnomAD 11-2165714-A-G, REVEL 0.69, CADD 24.80
- V367L (p.Val367Leu), gnomAD 11-2165748-C-G, REVEL 0.89, CADD 24.80
- L370H (p.Leu370His), gnomAD 11-2165762-A-AT, CADD 32.00
- L370P (p.Leu370Pro), gnomAD 11-2165762-A-G, REVEL 0.95, CADD 28.90
- L370V (p.Leu370Val), gnomAD 11-2165763-G-C, REVEL 0.56, CADD 16.00
- R373H (p.Arg373His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R373S (p.Arg373Ser), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10014, 1000Genomes rs555810288, ExAC rs555810288, Uncertain significance
- T374T (p.Thr374Thr), rs143405115, gnomAD 11-2165749-C-G, CADD 0.27
- T374M (p.Thr374Met), rs868563700, gnomAD 11-2165750-G-A, REVEL 0.96, AlphaMissense 0.58
- F375L (p.Phe375Leu), rs763198914, ClinGen CA379125954, ClinVar RCV002593546, ClinVar RCV004809847, AlphaMissense 0.99, MetaLR 0.19, Likely pathogenic, not provided; Autosomal recessive DOPA responsive dystonia
- F375F (p.Phe375Phe), rs769329337, gnomAD 11-2165740-G-A, CADD 0.45
- A376V (p.Ala376Val), UniProt VAR 072876, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- Q377* (p.Gln377Ter), rs2495800851, ClinGen CA379125945, ClinVar RCV003474110, Likely pathogenic
- Q380H (p.Gln380His), rs1846071715, gnomAD 11-2165725-C-G, REVEL 0.84, AlphaMissense 0.73
- Q380* (p.Gln380Ter), rs121917762, gnomAD 11-2165727-G-A, AlphaMissense 0.27, MetaLR 0.99
- Q380K (p.Gln380Lys), rs121917762, gnomAD 11-2165727-G-T, REVEL 0.81, AlphaMissense 0.27
- I382T (p.Ile382Thr), rs1554922725, ClinGen CA379125893, ClinVar RCV000668836, UniProt VAR 071719, AlphaMissense 0.75, MetaLR 0.99, Pathogenic/Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- G383G (p.Gly383Gly), rs758398302, gnomAD 11-2165719-C-T, CADD 0.20
- G383A (p.Gly383Ala), gnomAD 11-2165720-C-G, REVEL 0.83, CADD 22.90
- G383R (p.Gly383Arg), rs370962049, gnomAD 11-2165721-C-T, REVEL 0.91, AlphaMissense 0.46
- G383W (p.Gly383Trp), rs370962049, gnomAD 11-2165721-C-A, REVEL 0.82, AlphaMissense 0.46
- A385T (p.Ala385Thr), NCI-TCGA TCGA novel, Uncertain significance, Autosomal recessive DOPA responsive dystonia
- A385V (p.Ala385Val), rs763039181, ClinGen CA5818394, ClinVar RCV002222933, ClinVar RCV002466745, AlphaMissense 0.25, MetaLR 0.99, Conflicting interpretations, not specified; Autosomal recessive DOPA responsive dystonia; not provided
- L387M (p.Leu387Met), UniProt VAR 072878, Pathogenic, in ARSEGS
- G388G (p.Gly388Gly), rs545937773, gnomAD 11-2165677-C-T, CADD 7.82
- G388R (p.Gly388Arg), rs1264884607, gnomAD 11-2165679-C-T, REVEL 0.98, AlphaMissense 0.94
- G388E (p.Gly388Glu), rs796758678, gnomAD 11-2165696-C-T, REVEL 0.93, CADD 24.60
- G388D (p.Gly388Asp), gnomAD 11-2165702-C-T, REVEL 0.87, CADD 23.50
- A389A (p.Ala389Ala), rs199839852, gnomAD 11-2165698-G-C, CADD 0.18
- D391H (p.Asp391His), rs201996748, gnomAD 11-2165329-C-G, REVEL 0.76, CADD 23.70
- D391N (p.Asp391Asn), rs201996748, gnomAD 11-2165329-C-T, REVEL 0.51, CADD 22.30
- E392G (p.Glu392Gly), rs540601354, gnomAD 11-2165717-T-C, REVEL 0.42, CADD 22.60
- E392* (p.Glu392Ter), gnomAD 11-2165718-C-A, CADD 38.00
- I394T (p.Ile394Thr), UniProt VAR 072879, Likely pathogenic, Autosomal recessive DOPA responsive dystonia
- I394I (p.Ile394Ile), rs546226132, gnomAD 11-2165339-A-G, CADD 5.43
- I394F (p.Ile394Phe), rs1005978945, gnomAD 11-2165341-T-A, REVEL 0.28, CADD 12.90
- E395D (p.Glu395Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E395E (p.Glu395Glu), gnomAD 11-2165674-C-T, CADD 6.40
Public TH analysis runs
- TH analysis run — TH (465 variants) — completed 2026-08-18