TSC1 (Hamartin) variants and mutations
TSC1 (also known as Hamartin) is a human protein-coding gene encoding a hamartin protein. Together with TSC2, it restrains RHEB and mTORC1 signaling, preventing inappropriate cell growth when nutrients or growth signals are limited. Loss-of-function variants cause tuberous sclerosis complex with hamartomas and tumors in the brain, kidney, skin, heart, lungs, and other organs. This analysis covers 5,123 TSC1 variants and mutations. Of these, 47% have computational variant effect predictions. Disease context includes tuberous sclerosis, isolated focal cortical dysplasia type II, and tuberous sclerosis 1. Example TSC1 variants include M1?, M1I, and A2T.
Variant analysis overview
- Gene: TSC1
- Protein: Hamartin
- UniProt accession: Q92574
- Organism: Homo sapiens
- Variants analyzed: 5123
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 4,930 unspecified-consequence records; 9 in-frame deletions; 136 synonymous variants; 33 missense variants; 6 frameshift variants; 3 stop-gained variants; 1 in-frame insertions; 2 splice-region variants; 3 substitution
- Prediction scores: 2,429 variants have prediction scores (47% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: tuberous sclerosis, isolated focal cortical dysplasia type II, tuberous sclerosis 1, lymphangioleiomyomatosis, urinary bladder cancer, urinary bladder carcinoma, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, neurodegenerative disease, Seizure, cerebral cortical dysplasia, neurocutaneous syndrome.
Protein structure and variant hotspots
- Protein features: 6 post-translational modification sites.
- PTM context: 32 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, ClinGen, MaveDB, LitVar.
Notable TSC1 variants
Examples include M1?, M1I, A2T, A2V, Q3*, Q3R, Q4*, Q4H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV53766, cosmic curated COSV53763
- M1I (p.Met1Ile), rs2539147331, ClinGen CA375375474, ClinVar RCV004014206, Uncertain significance, Tuberous sclerosis syndrome
- A2T (p.Ala2Thr), rs2539147267, ClinGen CA375375471, ClinVar RCV003504631, Uncertain significance, Tuberous sclerosis 1
- A2V (p.Ala2Val), rs1588363746, ClinGen CA375375467, cosmic curated COSV10588, ClinVar RCV001296824, REVEL 0.48, CADD 24.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1; Lymphangiomyomato
- Q3* (p.Gln3Ter), rs2539147032, ClinGen CA375375463, ClinVar RCV003450557, Pathogenic
- Q3R (p.Gln3Arg), rs2539146983, ClinGen CA375375461, ClinVar RCV002376338, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q4* (p.Gln4Ter), rs753838459, ClinGen CA027033, ClinVar RCV000807651, ClinVar RCV003442093, CADD 36.00, Pathogenic
- Q4H (p.Gln4His), rs1588363707, ClinGen CA375375451, ClinVar RCV003505510, Uncertain significance, Tuberous sclerosis 1
- Q4K (p.Gln4Lys), rs753838459, ClinGen CA375375457, ClinVar RCV002430810, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q4P (p.Gln4Pro), rs2539146843, ClinGen CA375375454, ClinVar RCV003504695, ClinVar RCV004369366, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- A5T (p.Ala5Thr), rs2132297148, ClinGen CA375375450, ClinVar RCV002013000, Ensembl rs2132297148, REVEL 0.11, CADD 17.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- A5V (p.Ala5Val), Ensembl rs2132297110
- N6Y (p.Asn6Tyr), Ensembl rs2132297066
- V7I (p.Val7Ile), rs2539146331, ClinGen CA375375436, ClinVar RCV003615306, REVEL 0.15, CADD 3.13, Uncertain significance, Tuberous sclerosis 1
- G8A (p.Gly8Ala), rs1269896419, ClinGen CA375375427, ClinVar RCV000520247, ClinVar RCV000694959, REVEL 0.34, AlphaMissense 0.17, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- G8E (p.Gly8Glu), rs1269896419, ClinGen CA375375428, cosmic curated COSV53775, ClinVar RCV001886145, REVEL 0.42, AlphaMissense 0.17, Uncertain significance, Tuberous sclerosis 1
- G8R (p.Gly8Arg), rs773784532, ClinGen CA032066, cosmic curated COSV53763, ClinVar RCV001015114, REVEL 0.47, CADD 24.50, Conflicting interpretations, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome; Lymphangiomyomato
- G8V (p.Gly8Val), rs1269896419, ClinGen CA375375426, ClinVar RCV000703291, TOPMed rs1269896419, AlphaMissense 0.17, MetaLR 0.64, Uncertain significance, Tuberous sclerosis 1
- E9D (p.Glu9Asp), rs2539145878, ClinGen CA375375419, ClinVar RCV002441570, Uncertain significance, Hereditary cancer-predisposing syndrome
- E9G (p.Glu9Gly), TOPMed rs1431850441, Uncertain significance, Tuberous sclerosis 1
- E9K (p.Glu9Lys), rs1847040374, ClinGen CA375375423, ClinVar RCV003615161, Ensembl rs1847040374, AlphaMissense 0.22, MetaLR 0.61, Uncertain significance, Tuberous sclerosis 1
- E9Q (p.Glu9Gln), Ensembl rs1847040374, Uncertain significance
- L10F (p.Leu10Phe), rs1399717425, ClinGen CA375375415, ClinVar RCV000642023, ClinVar RCV001771877, REVEL 0.81, AlphaMissense 0.15, Conflicting interpretations, Tuberous sclerosis 1; not provided; Hereditary cancer-predisposing syndrome
- L10H (p.Leu10His), Ensembl rs1588363616
- L10I (p.Leu10Ile), rs1399717425, ClinGen CA375375417, ClinVar RCV001351635, TOPMed rs1399717425, AlphaMissense 0.15, MetaLR 0.90, Uncertain significance, Tuberous sclerosis 1
- L10R (p.Leu10Arg), Ensembl rs1588363616
- L11F (p.Leu11Phe), rs2539145698, ClinGen CA375375410, ClinVar RCV003615322, REVEL 0.56, CADD 22.60, Uncertain significance, Tuberous sclerosis 1
- A12G (p.Ala12Gly), Ensembl rs1588363595, Uncertain significance
- A12V (p.Ala12Val), rs1588363595, ClinGen CA375375400, NCI-TCGA Cosmic COSV5377, cosmic curated COSV53772, AlphaMissense 0.08, MetaLR 0.33, Uncertain significance, Tuberous sclerosis 1
- M13I (p.Met13Ile), rs2132296041, ClinGen CA375375395, ClinVar RCV001371801, ClinVar RCV002488173, AlphaMissense 0.39, MetaLR 0.73, Uncertain significance, Isolated focal cortical dysplasia type II; Tuberous sclerosis 1; Lymphangiomyoma
- M13L (p.Met13Leu), rs768147590, ClinGen CA375375399, ClinVar RCV002355163, ClinVar RCV003505217, AlphaMissense 0.09, MetaLR 0.38, Uncertain significance, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome
- M13T (p.Met13Thr), rs1041071543, ClinGen CA200902500, cosmic curated COSV10588, ClinVar RCV001021393, REVEL 0.50, CADD 23.40, Conflicting interpretations, Tuberous sclerosis syndrome; Hereditary cancer-predisposing syndrome; Tuberous s
- M13V (p.Met13Val), rs768147590, ClinGen CA037422, ClinVar RCV002020927, ExAC rs768147590, REVEL 0.31, AlphaMissense 0.09, Uncertain significance, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome
- L14P (p.Leu14Pro), rs2539145316, ClinGen CA375375389, ClinVar RCV003405755, Uncertain significance, TSC1-related disorder
- D15N (p.Asp15Asn), rs1554821020, ClinGen CA375375386, ClinVar RCV000561767, ClinVar RCV000697551, REVEL 0.40, CADD 24.80, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- D15Y (p.Asp15Tyr), rs1554821020, ClinGen CA375375385, ClinVar RCV003613927, REVEL 0.54, CADD 25.00, Uncertain significance, Tuberous sclerosis 1
- S16C (p.Ser16Cys), rs774900322, ClinGen CA037571, NCI-TCGA Cosmic COSV5376, cosmic curated COSV53766, REVEL 0.64, AlphaMissense 0.38, Uncertain significance, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome
- S16F (p.Ser16Phe), rs774900322, ClinGen CA375375375, ClinVar RCV000642044, ClinVar RCV001023078, AlphaMissense 0.38, MetaLR 0.85, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1; Tuberous sclerosi
- S16Y (p.Ser16Tyr), rs774900322, ClinGen CA375375376, ClinVar RCV003614994, AlphaMissense 0.38, MetaLR 0.85, Uncertain significance, Tuberous sclerosis 1
- P17R (p.Pro17Arg), rs1189239082, ClinGen CA375375370, ClinVar RCV002255908, ClinVar RCV003094218, REVEL 0.40, CADD 23.20, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- M18C (p.Met18Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- M18I (p.Met18Ile), rs940292214, NCI-TCGA TCGA novel, TOPMed rs940292214, ClinGen CA16612657, REVEL 0.14, CADD 6.64, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis syndrome; Tuberous s
- M18L (p.Met18Leu), rs762059806, ClinGen CA200902499, ClinVar RCV003615237, ClinVar RCV004950640, REVEL 0.13, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- M18T (p.Met18Thr), Ensembl rs2132295475, Uncertain significance, Hereditary cancer-predisposing syndrome
- M18V (p.Met18Val), rs762059806, ClinGen CA375375368, ClinVar RCV002344573, ClinVar RCV003102720, AlphaMissense 0.07, MetaLR 0.22, Conflicting interpretations, Tuberous sclerosis syndrome; Tuberous sclerosis 1
- L19Q (p.Leu19Gln), Ensembl rs1564504977, REVEL 0.79, CADD 24.60
- G20A (p.Gly20Ala), rs2132295150, ClinGen CA375375353, ClinVar RCV002299311, ClinVar RCV003223753, AlphaMissense 0.10, MetaLR 0.41, Uncertain significance, not provided; Tuberous sclerosis 1
- G20C (p.Gly20Cys), Ensembl rs2132295199, Likely benign
- G20D (p.Gly20Asp), rs2132295150, ClinGen CA375375351, ClinVar RCV003237460, ClinVar RCV003505185, AlphaMissense 0.10, MetaLR 0.41, Uncertain significance, Tuberous sclerosis 1; not provided
- G20R (p.Gly20Arg), rs2132295199, ClinGen CA375375355, ClinVar RCV001889352, ClinVar RCV005503227, AlphaMissense 0.07, MetaLR 0.25, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- G20S (p.Gly20Ser), rs2132295199, ClinGen CA375375356, cosmic curated COSV10732, ClinVar RCV001368315, AlphaMissense 0.07, MetaLR 0.25, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- V21L (p.Val21Leu), rs1392596033, ClinGen CA375375348, ClinVar RCV000795310, ClinVar RCV001572386, REVEL 0.39, CADD 18.80, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- R22L (p.Arg22Leu), ESP rs141736779, ExAC rs141736779, TOPMed rs141736779, gnomAD rs141736779, Benign, in FCORD2
- R22P (p.Arg22Pro), rs141736779, ClinGen CA375375343, ClinVar RCV000559688, ClinVar RCV006287203, REVEL 0.27, CADD 15.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- R22Q (p.Arg22Gln), rs141736779, ClinGen CA038390, cosmic curated COSV10966, ClinVar RCV000542889, REVEL 0.08, CADD 13.80, Conflicting interpretations, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome
- R22W (p.Arg22Trp), rs749030456, ClinGen CA038317, cosmic curated COSV53770, ClinVar RCV000477710, REVEL 0.47, CADD 24.60, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- D23G (p.Asp23Gly), rs1847034874, ClinGen CA375375337, ClinVar RCV001234163, Ensembl rs1847034874, REVEL 0.49, CADD 20.50, Uncertain significance, Tuberous sclerosis 1
- D23N (p.Asp23Asn), Ensembl rs2132294833, Uncertain significance, Hereditary cancer-predisposing syndrome
- D24N (p.Asp24Asn), rs984306144, ClinGen CA200902498, cosmic curated COSV53768, ClinVar RCV000815042, REVEL 0.39, CADD 20.80, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Lymphangiomyomatosis; Isolated focal co
- V25A (p.Val25Ala), cosmic curated COSV10588
- V25G (p.Val25Gly), rs2539143560, ClinGen CA375375321, ClinVar RCV002806708, Uncertain significance, Tuberous sclerosis 1
- V25M (p.Val25Met), rs1230244328, ClinGen CA375375324, cosmic curated COSV10588, ClinVar RCV000642002, REVEL 0.44, CADD 22.60, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- T26S (p.Thr26Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A27P (p.Ala27Pro), rs1847033606, ClinGen CA375375313, ClinVar RCV001207502, TOPMed rs1847033606, AlphaMissense 0.07, MetaLR 0.26, Uncertain significance, Tuberous sclerosis 1
- A27T (p.Ala27Thr), rs1847033606, ClinGen CA375375314, cosmic curated COSV53771, ClinVar RCV002419147, AlphaMissense 0.07, MetaLR 0.26, Uncertain significance, Hereditary cancer-predisposing syndrome
- A27V (p.Ala27Val), Ensembl rs2132294347, Uncertain significance, Hereditary cancer-predisposing syndrome
- V28D (p.Val28Asp), rs2539143116, ClinGen CA375375305, ClinVar RCV004015322, Uncertain significance, Tuberous sclerosis syndrome
- V28I (p.Val28Ile), Ensembl rs1588363318, Uncertain significance
- V28L (p.Val28Leu), rs1588363318, ClinGen CA375375307, ClinVar RCV000797675, Ensembl rs1588363318, AlphaMissense 0.07, MetaLR 0.40, Uncertain significance, Tuberous sclerosis 1
- F29C (p.Phe29Cys), rs2539143018, ClinGen CA2580079907, ClinVar RCV002481163, Pathogenic
- K30R (p.Lys30Arg), rs796053452, ClinGen CA319269, ClinVar RCV000189831, ClinVar RCV000230335, REVEL 0.23, CADD 19.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- E31D (p.Glu31Asp), rs781059342, ClinGen CA039811, NCI-TCGA Cosmic COSV5377, cosmic curated COSV53773, AlphaMissense 0.09, MetaLR 0.47, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- E31G (p.Glu31Gly), rs2539142669, ClinGen CA2580079904, ClinVar RCV003055327, Pathogenic
- E31Q (p.Glu31Gln), rs1847032440, ClinGen CA375375286, ClinVar RCV001209299, ClinVar RCV004010672, AlphaMissense 0.16, MetaLR 0.68, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis syndrome; Tuberous s
- N32K (p.Asn32Lys), rs1588363242, ClinGen CA375375274, ClinVar RCV001019650, Ensembl rs1588363242, AlphaMissense 0.33, MetaLR 0.55, Uncertain significance, Hereditary cancer-predisposing syndrome
- N32S (p.Asn32Ser), rs1222555421, ClinGen CA375375276, ClinVar RCV001340263, ClinVar RCV003169612, REVEL 0.08, CADD 19.00, Uncertain significance, Tuberous sclerosis syndrome; Tuberous sclerosis 1; Hereditary cancer-predisposin
- L33F (p.Leu33Phe), rs1847031671, ClinGen CA375375270, cosmic curated COSV53769, ClinVar RCV001067609, REVEL 0.68, CADD 26.50, Conflicting interpretations, Isolated focal cortical dysplasia type II; Tuberous sclerosis syndrome; Heredita
- L33H (p.Leu33His), Ensembl rs2132293706
- N34I (p.Asn34Ile), rs980870206, ClinGen CA200902497, ClinVar RCV002375824, ClinVar RCV003776284, AlphaMissense 0.06, MetaLR 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis syndrome; Tuberous s
- N34S (p.Asn34Ser), rs980870206, ClinGen CA375375262, ClinVar RCV000534666, ClinVar RCV002367854, REVEL 0.21, AlphaMissense 0.06, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- D36A (p.Asp36Ala), rs148468036, ClinGen CA375375240, ClinVar RCV003505837, AlphaMissense 0.28, MetaLR 0.75, Uncertain significance, Tuberous sclerosis 1
- D36E (p.Asp36Glu), rs886063624, ClinGen CA375375237, ClinVar RCV003296893, Ensembl rs886063624, AlphaMissense 0.14, MetaLR 0.34, Uncertain significance, Hereditary cancer-predisposing syndrome
- D36G (p.Asp36Gly), rs148468036, ClinGen CA375375239, ClinVar RCV001876614, ClinVar RCV004804258, AlphaMissense 0.28, MetaLR 0.75, Uncertain significance, not provided; Tuberous sclerosis syndrome; Tuberous sclerosis 1
- D36H (p.Asp36His), rs1847030850, ClinGen CA375375252, ClinVar RCV001052201, ClinVar RCV002256664, AlphaMissense 0.45, MetaLR 0.77, Uncertain significance, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome
- D36N (p.Asp36Asn), cosmic curated COSV53774
- D36V (p.Asp36Val), rs148468036, ClinGen CA027009, ClinVar RCV001347765, ClinVar RCV003375242, REVEL 0.71, AlphaMissense 0.28, Uncertain significance, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome
- R37C (p.Arg37Cys), rs1309560054, ClinGen CA375375235, cosmic curated COSV53772, ClinVar RCV000641995, REVEL 0.92, CADD 32.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- R37G (p.Arg37Gly), gnomAD rs1309560054, REVEL 0.93, CADD 29.10, Uncertain significance, Tuberous sclerosis 1
- R37H (p.Arg37His), rs750441497, ClinGen CA027051, cosmic curated COSV53771, ClinVar RCV000468501, REVEL 0.89, CADD 28.50, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- R37L (p.Arg37Leu), NCI-TCGA Cosmic COSV5377, REVEL 0.93, CADD 28.70, Uncertain significance, Hereditary cancer-predisposing syndrome
- R37P (p.Arg37Pro), ExAC rs750441497, TOPMed rs750441497, gnomAD rs750441497, Uncertain significance, Tuberous sclerosis 1
- R37S (p.Arg37Ser), rs1309560054, ClinGen CA375375234, ClinVar RCV000816480, ClinVar RCV001017290, REVEL 0.89, CADD 32.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Tuberous sclerosis syndro
- G38A (p.Gly38Ala), Ensembl rs2132271039
- G38C (p.Gly38Cys), rs1846929239, ClinGen CA375375229, ClinVar RCV001226460, ClinVar RCV002322096, AlphaMissense 0.88, MetaLR 0.79, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- G38D (p.Gly38Asp), Ensembl rs2132271039, REVEL 0.64, CADD 25.30, Uncertain significance, Tuberous sclerosis 1
- G38R (p.Gly38Arg), TOPMed rs1846929239, Uncertain significance, Tuberous sclerosis 1
- G38S (p.Gly38Ser), TOPMed rs1846929239, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1; not provided
- G38V (p.Gly38Val), Ensembl rs2132271039, Uncertain significance, Tuberous sclerosis 1
- P39A (p.Pro39Ala), rs1588359851, ClinGen CA375375225, ClinVar RCV000807843, ClinVar RCV004028633, REVEL 0.37, CADD 21.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- P39H (p.Pro39His), cosmic curated COSV53763, ExAC rs770831962, gnomAD rs770831962, Likely benign
- P39L (p.Pro39Leu), rs770831962, ClinGen CA375375221, ClinVar RCV002770406, ExAC rs770831962, AlphaMissense 0.28, MetaLR 0.79, Uncertain significance, Tuberous sclerosis 1
- P39R (p.Pro39Arg), rs770831962, ClinGen CA027217, ClinVar RCV000817725, ClinVar RCV004569733, REVEL 0.61, AlphaMissense 0.28, Conflicting interpretations, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome; Isolated focal co
- P39S (p.Pro39Ser), rs1588359851, ClinGen CA375375223, ClinVar RCV001239584, ClinVar RCV004034620, REVEL 0.24, CADD 19.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- M40I (p.Met40Ile), rs1480174819, ClinGen CA375375215, ClinVar RCV000804106, TOPMed rs1480174819, REVEL 0.28, CADD 21.90, Uncertain significance, Tuberous sclerosis 1
- M40V (p.Met40Val), rs974227401, ClinGen CA200902340, ClinVar RCV001368550, ClinVar RCV004681147, REVEL 0.26, CADD 15.30, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; Tuberous sclerosis 1
- L41F (p.Leu41Phe), rs118203334, ClinGen CA027330, ClinVar RCV000525235, ClinVar RCV001010403, REVEL 0.88, CADD 28.80, Conflicting interpretations, Hereditary cancer-predisposing syndrome; TSC1-related disorder; Tuberous scleros
- L41I (p.Leu41Ile), rs118203334, ClinGen CA004496, ClinVar RCV000034600, ClinVar RCV000054854, REVEL 0.77, CADD 27.20, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1; Isolated focal co
- L41V (p.Leu41Val), ESP rs118203334, ExAC rs118203334, TOPMed rs118203334, gnomAD rs118203334, Likely benign
- V42E (p.Val42Glu), rs1846926218, ClinGen CA375375204, ClinVar RCV001043370, Ensembl rs1846926218, AlphaMissense 0.97, MetaLR 0.82, Likely pathogenic, Tuberous sclerosis 1
- V42I (p.Val42Ile), ExAC rs777537794, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- V42L (p.Val42Leu), ExAC rs777537794
- N43D (p.Asn43Asp), Ensembl rs2132270154
- N43H (p.Asn43His), Ensembl rs2132270154
- N43I (p.Asn43Ile), Ensembl rs2132270083
- N43T (p.Asn43Thr), Ensembl rs2132270083
- N43Y (p.Asn43Tyr), Ensembl rs2132270154
- T44A (p.Thr44Ala), rs1399266964, ClinGen CA375375194, cosmic curated COSV10514, ClinVar RCV000550137, REVEL 0.12, CADD 18.50, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis syndrome; Tuberous s
- T44I (p.Thr44Ile), Ensembl rs2132269822
- T44P (p.Thr44Pro), cosmic curated COSV53766
- T44S (p.Thr44Ser), rs1399266964, ClinGen CA375375195, ClinVar RCV001010890, ClinVar RCV003614063, REVEL 0.11, CADD 15.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis syndrome; Tuberous s
- L45* (p.Leu45Ter), rs1554820662, ClinGen CA375375187, ClinVar RCV001530776, Ensembl rs1554820662, AlphaMissense 0.97, MetaLR 0.87, Pathogenic
- L45F (p.Leu45Phe), rs149278759, ESP rs149278759, ExAC rs149278759, TOPMed rs149278759, AlphaMissense 0.56, MetaLR 0.88, Uncertain significance, Tuberous sclerosis syndrome
- L45M (p.Leu45Met), ExAC rs755226092, TOPMed rs755226092, gnomAD rs755226092, Benign
- L45S (p.Leu45Ser), rs1554820662, ClinGen CA375375186, ClinVar RCV000642007, ClinVar RCV003432681, AlphaMissense 0.97, MetaLR 0.87, Conflicting interpretations, Tuberous sclerosis 1; not provided
- L45V (p.Leu45Val), rs755226092, ClinGen CA375375188, ClinVar RCV001974735, ClinVar RCV004804318, AlphaMissense 0.22, MetaLR 0.78, Uncertain significance, Isolated focal cortical dysplasia type II; Tuberous sclerosis 1
- L45W (p.Leu45Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V46E (p.Val46Glu), Ensembl rs2132269343
- V46L (p.Val46Leu), Ensembl rs2132269410
- V46M (p.Val46Met), Ensembl rs2132269410
- D47A (p.Asp47Ala), rs2539113178, ClinGen CA2580079896, ClinVar RCV002839375, ClinVar RCV004948804, Pathogenic
- D47E (p.Asp47Glu), rs2132269121, ClinGen CA375375169, ClinVar RCV002824214, Ensembl rs2132269121, AlphaMissense 0.32, MetaLR 0.68, Uncertain significance, Tuberous sclerosis 1
- D47G (p.Asp47Gly), NCI-TCGA Cosmic COSV5376, cosmic curated COSV53767, REVEL 0.97, CADD 32.00, Variant assessed as somatic; moderate impact.
- D47H (p.Asp47His), Ensembl rs2132269163
- D47N (p.Asp47Asn), cosmic curated COSV53774, Ensembl rs2132269163, REVEL 0.87, CADD 27.90
- D47Y (p.Asp47Tyr), Ensembl rs2132269163, Uncertain significance, Tuberous sclerosis 1
- Y48* (p.Tyr48Ter), rs2132269028, ClinGen CA375375161, ClinVar RCV003613744, Pathogenic
- Y48C (p.Tyr48Cys), rs2539113411, ClinGen CA375375164, ClinVar RCV003506366, Uncertain significance, Tuberous sclerosis 1
- Y48H (p.Tyr48His), cosmic curated COSV53774
- Y49* (p.Tyr49Ter), rs2539112315, ClinGen CA2580079895, ClinVar RCV003014116, Pathogenic
- Y49C (p.Tyr49Cys), rs2539113066, ClinGen CA375375156, ClinVar RCV003505716, Uncertain significance, Tuberous sclerosis 1
- Y49F (p.Tyr49Phe), rs2539113066, ClinGen CA375375155, ClinVar RCV003070413, ClinVar RCV004779430, Uncertain significance, not provided; Tuberous sclerosis 1
- Y49H (p.Tyr49His), TOPMed rs1407267988
- Y49N (p.Tyr49Asn), TOPMed rs1407267988
- L50M (p.Leu50Met), Ensembl rs2132268675, Uncertain significance
- L50P (p.Leu50Pro), rs118203341, ClinGen CA004957, ClinVar RCV000042040, ClinVar RCV002513612, AlphaMissense 0.32, MetaLR 0.84, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- L50Q (p.Leu50Gln), Ensembl rs118203341, Uncertain significance
- L50R (p.Leu50Arg), rs118203341, ClinGen CA375375149, ClinVar RCV002389885, AlphaMissense 0.32, MetaLR 0.84, Uncertain significance, Hereditary cancer-predisposing syndrome
- L50V (p.Leu50Val), rs2132268675, ClinGen CA375375151, ClinVar RCV001938000, ClinVar RCV002388820, AlphaMissense 0.11, MetaLR 0.75, Uncertain significance, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- E51D (p.Glu51Asp), rs118203342, ClinGen CA005036, ClinVar RCV000042047, ClinVar RCV000461171, REVEL 0.51, CADD 18.70, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; not specified
- E51K (p.Glu51Lys), cosmic curated COSV10646, Uncertain significance, in TSC1
- E51Q (p.Glu51Gln), rs1564503320, ClinGen CA375375147, ClinVar RCV002816247, ClinVar RCV005301190, REVEL 0.43, CADD 22.60, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- T52A (p.Thr52Ala), cosmic curated COSV53775, Ensembl rs2132268402
- T52S (p.Thr52Ser), Ensembl rs2132268402
- S53G (p.Ser53Gly), rs2539112262, ClinGen CA375375134, ClinVar RCV003614967, ClinVar RCV004371903, Uncertain significance, Tuberous sclerosis 1; Hereditary cancer-predisposing syndrome
- S53N (p.Ser53Asn), rs1588359592, ClinGen CA375375132, ClinVar RCV000816230, ClinVar RCV005749649, AlphaMissense 0.06, MetaLR 0.16, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- S53R (p.Ser53Arg), rs756335238, ExAC rs756335238, gnomAD rs756335238, ClinGen CA375375128, AlphaMissense 0.25, MetaLR 0.40, Uncertain significance, Hereditary cancer-predisposing syndrome
- S53T (p.Ser53Thr), rs1588359592, ClinGen CA375375131, ClinVar RCV003176665, ClinVar RCV004009631, AlphaMissense 0.06, MetaLR 0.16, Uncertain significance, Tuberous sclerosis syndrome; Hereditary cancer-predisposing syndrome
- S54C (p.Ser54Cys), rs1399121121, ClinGen CA375375124, ClinVar RCV003614402, gnomAD rs1399121121, REVEL 0.75, CADD 26.40, Likely benign, Tuberous sclerosis 1
- S54T (p.Ser54Thr), Ensembl rs2132268134
- Q55* (p.Gln55Ter), rs118203343, ClinGen CA005119, cosmic curated COSV53765, ClinVar RCV000042055, AlphaMissense 0.07, MetaLR 0.60, Pathogenic
- Q55E (p.Gln55Glu), Ensembl rs118203343, Pathogenic
- Q55H (p.Gln55His), Ensembl rs2132267841
- Q55L (p.Gln55Leu), Ensembl rs2132267915
- Q55R (p.Gln55Arg), Ensembl rs2132267915, Uncertain significance, Tuberous sclerosis 1
- P56A (p.Pro56Ala), TOPMed rs1330089369, gnomAD rs1330089369, Benign
- P56L (p.Pro56Leu), rs750512029, ClinGen CA029375, cosmic curated COSV10732, ClinVar RCV000444035, REVEL 0.38, CADD 19.30, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1; not provided
- P56R (p.Pro56Arg), ExAC rs750512029, TOPMed rs750512029, gnomAD rs750512029, Benign
- P56S (p.Pro56Ser), rs1330089369, ClinGen CA375375112, ClinVar RCV000558142, ClinVar RCV002404457, REVEL 0.38, CADD 17.80, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1; Isolated focal co
- A57G (p.Ala57Gly), Ensembl rs1846920951, Uncertain significance
- A57P (p.Ala57Pro), Ensembl rs1846921261
- A57S (p.Ala57Ser), Ensembl rs1846921261
- A57T (p.Ala57Thr), cosmic curated COSV53771, Ensembl rs1846921261, REVEL 0.31, CADD 19.10
- A57V (p.Ala57Val), rs1846920951, ClinGen CA375375104, ClinVar RCV004017050, Ensembl rs1846920951, REVEL 0.25, CADD 9.98, Uncertain significance, Tuberous sclerosis syndrome
- L58* (p.Leu58Ter), TOPMed rs1846919963, Uncertain significance
- L58F (p.Leu58Phe), Ensembl rs2132267222, Likely benign
- L58M (p.Leu58Met), Ensembl rs1564503254, Likely benign
- L58S (p.Leu58Ser), rs1846919963, ClinGen CA375375100, ClinVar RCV003474195, TOPMed rs1846919963, AlphaMissense 0.34, MetaLR 0.80, Uncertain significance, Isolated focal cortical dysplasia type II; Hereditary cancer-predisposing syndro
- H59D (p.His59Asp), Ensembl rs2132267151, Uncertain significance
- H59L (p.His59Leu), rs757837986, ClinGen CA029689, ClinVar RCV001518037, ClinVar RCV005749674, REVEL 0.41, AlphaMissense 0.28, Benign/Likely benign, Hereditary cancer-predisposing syndrome; Tuberous sclerosis 1
- H59N (p.His59Asn), cosmic curated COSV10966
Public TSC1 analysis runs
- TSC1 analysis run — TSC1 (5,123 variants) — completed 2026-08-19