NOTCH1 (P46531) variants and mutations
NOTCH1 (also known as P46531) is a human protein-coding gene encoding a neurogenic locus notch homolog protein 1 protein. Ligand-dependent cleavage releases an intracellular domain that directly controls transcriptional programs governing cell fate and differentiation. Pathogenic variants can cause congenital aortic-valve disease and left-sided heart defects, while activating or inactivating somatic changes contribute to several cancers. This analysis covers 10,057 NOTCH1 variants and mutations. Of these, 41% have computational variant effect predictions. Disease context includes Adams-Oliver syndrome, B-cell chronic lymphocytic leukemia, and aortic stenosis. Example NOTCH1 variants include M1L, P2A, and P2S.
Variant analysis overview
- Gene: NOTCH1
- Protein: P46531
- UniProt accession: P46531
- Organism: Homo sapiens
- Variants analyzed: 10057
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 9,698 unspecified-consequence records; 1 stop retained variant; 207 synonymous variants; 134 missense variants; 4 stop-gained variants; 5 in-frame deletions; 4 frameshift variants; 2 in-frame insertions; 1 substitution
- Prediction scores: 4,074 variants have prediction scores (41% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Adams-Oliver syndrome, B-cell chronic lymphocytic leukemia, aortic stenosis, cancer, head and neck squamous cell carcinoma, lymphoid leukemia, familial thoracic aortic aneurysm and aortic dissection, neurodegenerative disease, squamous cell lung carcinoma, cervical squamous cell carcinoma, hereditary disease, Rare disease with thoracic aortic aneurysm and aortic dissection.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 36 domains; 16 binding sites; 50 post-translational modification sites.
- Structural context: 5,178 variants have structural context.
- PTM context: 171 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable NOTCH1 variants
Examples include M1L, P2A, P2S, P3L, P3R, L4P, A6E, A6S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs2133408684, ClinGen CA375579939, ClinVar RCV001782535, MetaLR 0.19, MetaSVM -0.90, Likely pathogenic, not provided
- P2A (p.Pro2Ala), rs975429231, ClinGen CA201608708, ClinVar RCV000693595, TOPMed rs975429231, CADD 20.80, PolyPhen-2 0.00, Benign, Adams-Oliver syndrome 5
- P2S (p.Pro2Ser), TOPMed rs975429231, gnomAD rs975429231, CADD 21.90, PolyPhen-2 0.01, Benign
- P3L (p.Pro3Leu), TOPMed rs1229360786, CADD 19.30, PolyPhen-2 0.00, Uncertain significance, Adams-Oliver syndrome 5
- P3R (p.Pro3Arg), TOPMed rs1229360786, CADD 19.70, PolyPhen-2 0.00
- L4P (p.Leu4Pro), rs1260556792, ClinGen CA375579906, ClinVar RCV004534469, TOPMed rs1260556792, CADD 23.20, PolyPhen-2 0.00, Uncertain significance, NOTCH1-related disorder
- A6E (p.Ala6Glu), rs758139292, ClinGen CA375579890, ClinVar RCV003748018, CADD 21.90, PolyPhen-2 0.06, Uncertain significance, Adams-Oliver syndrome 5
- A6S (p.Ala6Ser), rs1564217184, ClinGen CA375579895, ClinVar RCV003172271, CADD 15.80, PolyPhen-2 0.01, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- A6T (p.Ala6Thr), rs1564217184, ClinGen CA375579892, ClinVar RCV000697592, TOPMed rs1564217184, CADD 17.30, PolyPhen-2 0.00, Uncertain significance, Adams-Oliver syndrome 5
- A6V (p.Ala6Val), rs878855023, ClinGen CA10582650, ClinVar RCV000230821, ClinVar RCV000769619, CADD 22.60, PolyPhen-2 0.00, Likely benign, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- P7L (p.Pro7Leu), rs1554733804, ClinGen CA375579881, ClinVar RCV000532252, Ensembl rs1554733804, CADD 21.20, PolyPhen-2 0.00, Uncertain significance, Adams-Oliver syndrome 5
- P7S (p.Pro7Ser), rs1397523469, ClinGen CA375579885, ClinVar RCV000802034, ClinVar RCV002270917, CADD 22.50, PolyPhen-2 0.24, Uncertain significance, Adams-Oliver syndrome 5
- P7T (p.Pro7Thr), rs1397523469, ClinGen CA375579887, ClinVar RCV001772648, TOPMed rs1397523469, CADD 22.20, PolyPhen-2 0.19, Uncertain significance, not provided
- C10R (p.Cys10Arg), Ensembl rs2133408626, CADD 22.60, PolyPhen-2 0.15
- C10Y (p.Cys10Tyr), rs1843806739, ClinGen CA375579858, ClinVar RCV001757150, TOPMed rs1843806739, CADD 22.20, PolyPhen-2 0.36, Uncertain significance, not provided
- L11R (p.Leu11Arg), rs2133408615, ClinGen CA375579841, ClinVar RCV001751993, Ensembl rs2133408615, MetaLR 0.37, MetaSVM -0.78, Uncertain significance, not provided
- L11V (p.Leu11Val), TOPMed rs1254279627
- A12V (p.Ala12Val), rs1473062369, ClinGen CA375579834, ClinVar RCV001765924, ClinVar RCV001868647, CADD 19.10, PolyPhen-2 0.00, Uncertain significance, Adams-Oliver syndrome 5; not provided; Aortic valve disease 1
- P15R (p.Pro15Arg), rs2540494904, ClinGen CA375579809, ClinVar RCV003587555, CADD 20.40, PolyPhen-2 0.08, Uncertain significance, Adams-Oliver syndrome 5
- A16T (p.Ala16Thr), rs2133408578, ClinGen CA375579805, ClinVar RCV001806589, Ensembl rs2133408578, CADD 18.90, PolyPhen-2 0.06, Uncertain significance, not provided
- L17P (p.Leu17Pro), Ensembl rs2133408570, CADD 21.00, PolyPhen-2 0.00
- A18T (p.Ala18Thr), rs754613772, ClinGen CA5342272, ClinVar RCV001648232, ClinVar RCV002072991, CADD 21.60, PolyPhen-2 0.08, Benign, Adams-Oliver syndrome 5; Aortic valve disease 1; not provided
- A19S (p.Ala19Ser), TOPMed rs1843806277, CADD 18.80, PolyPhen-2 0.01
- A19T (p.Ala19Thr), TOPMed rs1843806277, CADD 21.30, PolyPhen-2 0.10
- R20L (p.Arg20Leu), rs1554733799, ClinGen CA375579751, ClinVar RCV001855279, ClinVar RCV002270877, CADD 23.20, PolyPhen-2 0.04, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Adams-Oliver syndrome 5
- G21D (p.Gly21Asp), rs1554733407, ClinGen CA375579362, ClinVar RCV000523036, Ensembl rs1554733407, CADD 27.10, PolyPhen-2 0.72, Uncertain significance, not provided
- G21V (p.Gly21Val), NCI-TCGA Cosmic COSV5308, CADD 29.10, PolyPhen-2 0.84, Variant assessed as somatic; moderate impact.
- P22L (p.Pro22Leu), rs769046407, ClinGen CA5342263, ClinVar RCV002364561, ClinVar RCV002463204, CADD 11.40, PolyPhen-2 0.00, Conflicting interpretations, Adams-Oliver syndrome 5; not provided; Familial thoracic aortic aneurysm and aor
- P22R (p.Pro22Arg), rs769046407, ClinGen CA375579341, ClinVar RCV003869791, ExAC rs769046407, CADD 19.10, Uncertain significance, Adams-Oliver syndrome 5
- P22S (p.Pro22Ser), rs114832250, ClinGen CA161173, ClinVar RCV000121673, ClinVar RCV000232532, CADD 22.40, PolyPhen-2 0.02, Benign/Likely benign, Adams-Oliver syndrome 5; not specified; not provided
- R23L (p.Arg23Leu), rs869025260, ClinGen CA351614, ClinVar RCV000207428, gnomAD rs869025260, CADD 22.90, PolyPhen-2 0.27, Likely benign, Anophthalmia-microphthalmia syndrome
- R23P (p.Arg23Pro), rs869025260, ClinGen CA375579313, ClinVar RCV002001927, ClinVar RCV002370567, CADD 24.10, PolyPhen-2 0.61, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Adams-Oliver syndrome 5
- C24Y (p.Cys24Tyr), Ensembl rs2133406274, CADD 26.40, PolyPhen-2 0.73
- S25F (p.Ser25Phe), TOPMed rs1843774930, CADD 23.10, PolyPhen-2 0.23
- Q26* (p.Gln26Ter), gnomAD rs1217905346, CADD 41.00
- Q26H (p.Gln26His), Ensembl rs2133406259, CADD 22.40, PolyPhen-2 0.36
- Q26R (p.Gln26Arg), gnomAD rs1843774844, CADD 22.60, PolyPhen-2 0.00
- P27S (p.Pro27Ser), ExAC rs769784635, TOPMed rs769784635, gnomAD rs769784635, CADD 19.80, PolyPhen-2 0.04, Uncertain significance, not provided
- P27T (p.Pro27Thr), rs769784635, ClinGen CA5342260, ClinVar RCV000462159, ClinVar RCV002418394, CADD 18.90, PolyPhen-2 0.00, Conflicting interpretations, Adams-Oliver syndrome 5; not specified; Familial thoracic aortic aneurysm and ao
- G28R (p.Gly28Arg), TOPMed rs1388609508, gnomAD rs1388609508, Likely benign
- G28S (p.Gly28Ser), rs1388609508, ClinGen CA375579239, ClinVar RCV002430338, ClinVar RCV004529136, CADD 5.91, PolyPhen-2 0.00, Conflicting interpretations, NOTCH1-related disorder; Familial thoracic aortic aneurysm and aortic dissection
- E29D (p.Glu29Asp), rs1843774562, ClinGen CA375579205, ClinVar RCV003341810, gnomAD rs1843774562, CADD 15.00, PolyPhen-2 0.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- E29K (p.Glu29Lys), gnomAD rs908111363, CADD 23.20, PolyPhen-2 0.13
- C31R (p.Cys31Arg), NCI-TCGA TCGA novel, CADD 29.40, PolyPhen-2 1.00, Variant assessed as somatic; moderate impact.
- C31W (p.Cys31Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C31Y (p.Cys31Tyr), gnomAD rs1293196350, CADD 26.80, PolyPhen-2 1.00
- L32V (p.Leu32Val), ESP rs367858719, ExAC rs367858719, TOPMed rs367858719, gnomAD rs367858719, CADD 4.91, PolyPhen-2 0.10, Likely benign
- N33S (p.Asn33Ser), rs2133406228, ClinGen CA375579103, ClinVar RCV001981025, Ensembl rs2133406228, MetaLR 0.15, MetaSVM -0.78, Uncertain significance, Adams-Oliver syndrome 5
- G34S (p.Gly34Ser), gnomAD rs1402866125, CADD 27.30, PolyPhen-2 0.86
- G34V (p.Gly34Val), Ensembl rs1197823538, CADD 26.50, PolyPhen-2 0.93
- G35E (p.Gly35Glu), Ensembl rs2133406206
- G35R (p.Gly35Arg), rs1843774247, ClinGen CA375579057, ClinVar RCV001216503, Ensembl rs1843774247, CADD 27.50, PolyPhen-2 1.00, Uncertain significance, Adams-Oliver syndrome 5
- K36E (p.Lys36Glu), Ensembl rs1589084110
- C37R (p.Cys37Arg), gnomAD rs1172832489, CADD 29.70, PolyPhen-2 1.00
- E38K (p.Glu38Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A39V (p.Ala39Val), 1000Genomes rs747994799, ExAC rs747994799, gnomAD rs747994799, CADD 13.10, PolyPhen-2 0.00, Likely benign, Familial thoracic aortic aneurysm and aortic dissection
- A40D (p.Ala40Asp), gnomAD rs1433296087, CADD 9.76, PolyPhen-2 0.00
- A40G (p.Ala40Gly), gnomAD rs1433296087
- A40T (p.Ala40Thr), Ensembl rs2133406180, CADD 13.20, PolyPhen-2 0.00
- A40V (p.Ala40Val), NCI-TCGA TCGA novel, CADD 13.20, PolyPhen-2 0.02, Variant assessed as somatic; moderate impact.
- N41S (p.Asn41Ser), ExAC rs778658796, gnomAD rs778658796, CADD 22.60, PolyPhen-2 0.00, Uncertain significance, Adams-Oliver syndrome 5
- G42A (p.Gly42Ala), ExAC rs754666783, gnomAD rs754666783
- G42D (p.Gly42Asp), ExAC rs754666783, gnomAD rs754666783, CADD 24.50, PolyPhen-2 0.95, Benign, Adams-Oliver syndrome 5
- G42V (p.Gly42Val), rs754666783, ClinGen CA375578785, ClinVar RCV003313560, CADD 26.30, PolyPhen-2 0.95, Uncertain significance, not provided
- T43A (p.Thr43Ala), ExAC rs753523233, TOPMed rs753523233, gnomAD rs753523233, CADD 22.20, PolyPhen-2 0.11
- T43M (p.Thr43Met), rs371103280, ClinGen CA5342252, ClinVar RCV000519931, ClinVar RCV002384008, CADD 29.70, PolyPhen-2 0.71, Conflicting interpretations, Adams-Oliver syndrome 5; not provided; Familial thoracic aortic aneurysm and aor
- T43S (p.Thr43Ser), ExAC rs753523233, TOPMed rs753523233, gnomAD rs753523233, CADD 21.20, PolyPhen-2 0.08
- A45T (p.Ala45Thr), Ensembl rs2133406144
- C46Y (p.Cys46Tyr), rs2540492460, ClinGen CA375578709, ClinVar RCV003225302, CADD 28.30, PolyPhen-2 1.00, Uncertain significance, not provided
- V47I (p.Val47Ile), gnomAD rs1331779957, CADD 11.10, PolyPhen-2 0.00
- V47L (p.Val47Leu), rs1331779957, ClinGen CA375578682, ClinVar RCV002389216, CADD 10.50, PolyPhen-2 0.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- C48* (p.Cys48Ter), Ensembl rs2133379881
- C48F (p.Cys48Phe), Ensembl rs1327257445
- C48R (p.Cys48Arg), Ensembl rs2133379887, Uncertain significance
- C48S (p.Cys48Ser), Ensembl rs1327257445, Uncertain significance, Adams-Oliver syndrome 5
- C48W (p.Cys48Trp), Ensembl rs2133379881
- C48Y (p.Cys48Tyr), Ensembl rs1327257445
- G49A (p.Gly49Ala), Ensembl rs2133379875
- G49C (p.Gly49Cys), Ensembl rs2133379880, CADD 14.10, PolyPhen-2 0.40
- G49D (p.Gly49Asp), Ensembl rs2133379875, CADD 10.10, PolyPhen-2 0.05
- G49S (p.Gly49Ser), Ensembl rs2133379880, CADD 5.37, PolyPhen-2 0.00
- G49V (p.Gly49Val), Ensembl rs2133379875, CADD 11.50, PolyPhen-2 0.01
- G50A (p.Gly50Ala), Ensembl rs2133379870
- G50E (p.Gly50Glu), Ensembl rs2133379870, CADD 10.20, PolyPhen-2 0.08
- G50R (p.Gly50Arg), rs776758626, ExAC rs776758626, TOPMed rs776758626, gnomAD rs776758626, CADD 16.60, PolyPhen-2 0.32, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Adams-Oliver syndrome 5
- G50V (p.Gly50Val), Ensembl rs2133379870, CADD 14.20, PolyPhen-2 0.00
- A51D (p.Ala51Asp), rs771954465, ClinGen CA5342240, ClinVar RCV000798007, ExAC rs771954465, CADD 20.90, PolyPhen-2 0.00, Uncertain significance, Adams-Oliver syndrome 5
- A51S (p.Ala51Ser), gnomAD rs1188063786, CADD 17.40, PolyPhen-2 0.00
- A51T (p.Ala51Thr), gnomAD rs1188063786, CADD 22.30, PolyPhen-2 0.03
- F52C (p.Phe52Cys), Ensembl rs2133379838
- F52I (p.Phe52Ile), Ensembl rs2133379846, Uncertain significance, Adams-Oliver syndrome 5
- F52L (p.Phe52Leu), Ensembl rs2133379846, CADD 8.92, PolyPhen-2 0.05, Benign
- F52S (p.Phe52Ser), Ensembl rs2133379838
- F52V (p.Phe52Val), Ensembl rs2133379846
- F52Y (p.Phe52Tyr), Ensembl rs2133379838
- V53A (p.Val53Ala), Ensembl rs2133379824
- V53E (p.Val53Glu), Ensembl rs2133379824
- V53G (p.Val53Gly), Ensembl rs2133379824
- V53L (p.Val53Leu), ExAC rs757497167, TOPMed rs757497167, gnomAD rs757497167, CADD 14.40, PolyPhen-2 0.01, Uncertain significance
- V53M (p.Val53Met), rs757497167, ClinGen CA5342237, NCI-TCGA Cosmic COSV5305, ClinVar RCV000477441, CADD 21.10, PolyPhen-2 0.05, Conflicting interpretations, Adams-Oliver syndrome 5; not provided; Familial thoracic aortic aneurysm and aor
- G54A (p.Gly54Ala), Ensembl rs2133379818
- G54C (p.Gly54Cys), TOPMed rs1843418768, CADD 27.50, PolyPhen-2 1.00
- G54D (p.Gly54Asp), Ensembl rs2133379818, CADD 25.70, PolyPhen-2 1.00
- G54R (p.Gly54Arg), TOPMed rs1843418768
- G54S (p.Gly54Ser), TOPMed rs1843418768
- G54V (p.Gly54Val), Ensembl rs2133379818, CADD 25.50, PolyPhen-2 1.00
- P55A (p.Pro55Ala), Ensembl rs2133379809
- P55L (p.Pro55Leu), rs1286892980, ClinGen CA375573184, ClinVar RCV003121238, gnomAD rs1286892980, MetaLR 0.04, MetaSVM -1.02, Benign, Adams-Oliver syndrome 5
- P55Q (p.Pro55Gln), gnomAD rs1286892980, MetaLR 0.04, MetaSVM -1.02, Benign
- P55R (p.Pro55Arg), rs1286892980, ClinGen CA375573185, ClinVar RCV002395029, gnomAD rs1286892980, MetaLR 0.04, MetaSVM -1.02, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- P55S (p.Pro55Ser), Ensembl rs2133379809
- P55T (p.Pro55Thr), Ensembl rs2133379809, CADD 19.40, PolyPhen-2 0.01
- R56* (p.Arg56Ter), rs1348892740, ClinGen CA375573182, ClinVar RCV000624179, ClinVar RCV003228963, CADD 36.00, Pathogenic
- R56G (p.Arg56Gly), gnomAD rs1348892740, Pathogenic
- R56L (p.Arg56Leu), TOPMed rs1286309175, gnomAD rs1286309175, CADD 16.40, PolyPhen-2 0.00, Benign
- R56P (p.Arg56Pro), TOPMed rs1286309175, gnomAD rs1286309175, CADD 22.40, PolyPhen-2 0.48, Benign
- R56Q (p.Arg56Gln), rs1286309175, ClinGen CA375573180, ClinVar RCV003748514, ClinVar RCV005387211, CADD 17.80, PolyPhen-2 0.00, Conflicting interpretations, Adams-Oliver syndrome 5; Familial thoracic aortic aneurysm and aortic dissection
- C57* (p.Cys57Ter), Ensembl rs2133379767, CADD 38.00
- C57G (p.Cys57Gly), Ensembl rs2133379780
- C57S (p.Cys57Ser), Ensembl rs2133379776, Uncertain significance
- C57W (p.Cys57Trp), Ensembl rs2133379767
- C57Y (p.Cys57Tyr), rs2133379776, ClinGen CA375573175, ClinVar RCV003748655, Ensembl rs2133379776, CADD 26.60, PolyPhen-2 1.00, Uncertain significance, Adams-Oliver syndrome 5
- Q58* (p.Gln58Ter), gnomAD rs1340326048
- Q58E (p.Gln58Glu), gnomAD rs1340326048, CADD 24.00, PolyPhen-2 0.98
- Q58H (p.Gln58His), TOPMed rs1353567476, gnomAD rs1353567476, CADD 23.20, PolyPhen-2 1.00
- Q58K (p.Gln58Lys), gnomAD rs1340326048, CADD 26.40, PolyPhen-2 0.98
- D59A (p.Asp59Ala), Ensembl rs2133379743
- D59E (p.Asp59Glu), Ensembl rs2133379737, CADD 4.43, PolyPhen-2 0.03
- D59G (p.Asp59Gly), Ensembl rs2133379743
- D59H (p.Asp59His), Ensembl rs2133379750
- D59N (p.Asp59Asn), Ensembl rs2133379750
- D59V (p.Asp59Val), Ensembl rs2133379743
- D59Y (p.Asp59Tyr), Ensembl rs2133379750
- P60A (p.Pro60Ala), ExAC rs755775484, TOPMed rs755775484, gnomAD rs755775484, Benign
- P60H (p.Pro60His), Ensembl rs2133379729, CADD 19.20, PolyPhen-2 0.01
- P60L (p.Pro60Leu), Ensembl rs2133379729, CADD 20.40, PolyPhen-2 0.15, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- P60R (p.Pro60Arg), Ensembl rs2133379729
- P60S (p.Pro60Ser), ExAC rs755775484, TOPMed rs755775484, gnomAD rs755775484, CADD 10.40, PolyPhen-2 0.01, Benign, Adams-Oliver syndrome 5
- P60T (p.Pro60Thr), rs755775484, ClinGen CA5342234, ClinVar RCV003587488, ClinVar RCV004636776, CADD 11.50, PolyPhen-2 0.11, Conflicting interpretations, Adams-Oliver syndrome 5; Familial thoracic aortic aneurysm and aortic dissection
- N61I (p.Asn61Ile), TOPMed rs1554730749, gnomAD rs1554730749, Likely benign
- N61S (p.Asn61Ser), rs1554730749, ClinGen CA375573144, ClinVar RCV002306361, ClinVar RCV004047729, CADD 11.20, PolyPhen-2 0.01, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; not provided
- N61T (p.Asn61Thr), TOPMed rs1554730749, gnomAD rs1554730749, Likely benign
- P62A (p.Pro62Ala), Ensembl rs2133379715
- P62L (p.Pro62Leu), ExAC rs749947050, gnomAD rs749947050, CADD 27.80, PolyPhen-2 1.00
- P62Q (p.Pro62Gln), ExAC rs749947050, gnomAD rs749947050, CADD 26.90, PolyPhen-2 1.00
- P62R (p.Pro62Arg), ExAC rs749947050, gnomAD rs749947050
- P62S (p.Pro62Ser), Ensembl rs2133379715, CADD 26.90, PolyPhen-2 1.00
- C63F (p.Cys63Phe), Ensembl rs2133379703, CADD 26.90, PolyPhen-2 1.00
- C63G (p.Cys63Gly), Ensembl rs2133379705
- C63R (p.Cys63Arg), Ensembl rs2133379705
- C63S (p.Cys63Ser), Ensembl rs2133379703
- C63W (p.Cys63Trp), Ensembl rs2133379700
- C63Y (p.Cys63Tyr), Ensembl rs2133379703
- L64F (p.Leu64Phe), Ensembl rs2133379694
- L64H (p.Leu64His), Ensembl rs2133379692
- L64I (p.Leu64Ile), Ensembl rs2133379694
- L64P (p.Leu64Pro), Ensembl rs2133379692
- S65C (p.Ser65Cys), Ensembl rs2133379689
- S65G (p.Ser65Gly), Ensembl rs2133379689, CADD 22.40, PolyPhen-2 0.19
- S65N (p.Ser65Asn), Ensembl rs2133379686, CADD 19.70, PolyPhen-2 0.01
- S65R (p.Ser65Arg), Ensembl rs2133379678, NCI-TCGA Cosmic COSV5308, Variant assessed as somatic; moderate impact.
- S65T (p.Ser65Thr), Ensembl rs2133379686
- T66A (p.Thr66Ala), Ensembl rs2133379675
- T66I (p.Thr66Ile), rs752133245, ClinGen CA5342230, ClinVar RCV001719048, ClinVar RCV003586204, CADD 10.70, PolyPhen-2 0.17, Benign/Likely benign, Adams-Oliver syndrome 5; not provided
- T66N (p.Thr66Asn), NCI-TCGA Cosmic COSV5308, NCI-TCGA Cosmic COSV9948, CADD 5.00, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- T66P (p.Thr66Pro), Ensembl rs2133379675
- T66S (p.Thr66Ser), Ensembl rs2133379675, CADD 2.46, PolyPhen-2 0.01
- P67A (p.Pro67Ala), Ensembl rs2133379665, Uncertain significance
- P67H (p.Pro67His), Ensembl rs1843418088, Uncertain significance
- P67L (p.Pro67Leu), rs1843418088, ClinGen CA375573081, ClinVar RCV003586565, Ensembl rs1843418088, MetaLR 0.40, MetaSVM -0.27, Uncertain significance, Adams-Oliver syndrome 5
- P67R (p.Pro67Arg), Ensembl rs1843418088, Uncertain significance
- P67S (p.Pro67Ser), rs2133379665, ClinGen CA375573086, ClinVar RCV003055681, Ensembl rs2133379665, CADD 23.60, PolyPhen-2 0.64, Uncertain significance, Adams-Oliver syndrome 5
- P67T (p.Pro67Thr), NCI-TCGA Cosmic COSV5305, NCI-TCGA Cosmic COSV5309, Ensembl rs2133379665, Uncertain significance
- C68F (p.Cys68Phe), Ensembl rs2133379652, CADD 26.00, PolyPhen-2 1.00
- C68S (p.Cys68Ser), Ensembl rs2133379652
- C68W (p.Cys68Trp), Ensembl rs2133379647
- C68Y (p.Cys68Tyr), NCI-TCGA Cosmic COSV5304, NCI-TCGA Cosmic COSV9948, Ensembl rs2133379652, CADD 25.80, PolyPhen-2 1.00, Variant assessed as somatic; moderate impact.
- K69* (p.Lys69Ter), Ensembl rs2133379644
- K69E (p.Lys69Glu), Ensembl rs2133379644, CADD 18.20, PolyPhen-2 0.34
- K69M (p.Lys69Met), Ensembl rs2133379639
Public NOTCH1 analysis runs
- NOTCH1 analysis run — NOTCH1 (10,057 variants) — completed 2026-08-19