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NOTCH1
Variants
VariantGeneTypeCOSMIC IDDNA Change (Coding Nucleotide)Exon
NOTCH1 exon(s) 26 missenseNOTCH1missense26
NOTCH1 exon(s) 27 missenseNOTCH1missense27
NOTCH1 exon(s) 34 frameshiftNOTCH1frameshift34
NOTCH1 exon(s) 34 nonsenseNOTCH1nonsense34
NOTCH1 exon(s) 34 missenseNOTCH1missense34
NOTCH1 exon(s) 26 insertionNOTCH1insertion26
NOTCH1 exon(s) 26 deletionNOTCH1deletion26
NOTCH1 exon(s) 27 insertionNOTCH1insertion27
NOTCH1 exon(s) 27 deletionNOTCH1deletion27
NOTCH1 copy number gainNOTCH1CNV
NOTCH1 copy number lossNOTCH1CNV
NOTCH1 any mutationNOTCH1any
NOTCH1 L2457VNOTCH1missense34
NOTCH1 exon(s) 26-27 deletionNOTCH1deletion26-27

Interpretations

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Tier 2
NOTCH1
Variants
NOTCH1 exon(s) 26 missense
NOTCH1 exon(s) 27 missense
NOTCH1 exon(s) 34 frameshift
NOTCH1 exon(s) 34 nonsense
NOTCH1 exon(s) 34 missense
NOTCH1 exon(s) 26 insertion
NOTCH1 exon(s) 26 deletion
NOTCH1 exon(s) 27 insertion
NOTCH1 exon(s) 27 deletion
Primary Sites
Blood
Bone Marrow
Tumor Types
T Lymphoblastic Leukemia/Lymphoma
Acute Leukemia of Unspecified Cell Type
Acute Myeloid Leukemia
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic Syndrome
Myelodysplastic/Myeloproliferative Neoplasm
Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
Primary Myelofibrosis
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

NOTCH1 encodes a member of the NOTCH family of proteins, which is a group of transmembrane receptors involved in the Notch signaling pathway. Notch signaling regulates cell fate decisions during development, and plays a crucial role in T cell development. Activating mutations of NOTCH1 including missense mutations and inframe inserstions/deletions in the heterodimerization(HD) domains either alone or together with missense, nonsense or frameshift (in/del) mutations in the C terminal PEST domain have been described in approximately 50% of cases of T-ALL. The HD domain or PEST domain mutations may occur together in cis (on the same allele) in ALL. NOTCH1 mutations are very rare in AML. However, NOTCH1 mutations are present in about 27% patients with T-myeloid mixed-phenotypeacute leukemia. The potential utility of therapeutic targeting of activating NOTCH1 mutations in these diseases remains to be elucidated.

Last updated: 2018-11-12 20:40:47 UTC
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Tier 1
NOTCH1
Variants
NOTCH1 exon(s) 34 frameshift
NOTCH1 exon(s) 34 nonsense
NOTCH1 exon(s) 34 missense
Primary Sites
Blood
Bone Marrow
Tumor Types
Chronic Lymphocytic Leukemia
Interpretation

NOTCH1 mutations have also recently been reported in approximately 10% of chronic lymphocytic leukemia and are typically PEST domain mutations in that disease. In CLL, NOTCH1 mutations and tend to be exlusive of SF3B1 mutations and possibly TP53 mutations, although some studies demonstrate that NOTCH1 mutations are associated with mutations of TP53. In CLL, the presence of NOTCH1 mutations has been associated with trisomy 12 and aggressive biologic features(CD38+, ZAP70+, unmutated IgH variable region) and adverse prognosis in some settings. The potential utility of therapeutic targeting of activating NOTCH1 mutations in these diseases remains to be elucidated.

Last updated: 2016-06-04 23:28:05 UTC
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Tier 2
NOTCH1
Variants
NOTCH1 copy number gain
NOTCH1 copy number loss
Primary Sites
Adrenal Gland
Anus
Ampulla (Pancreaticobiliary Duct)
Appendix
Bladder
Blood
Bone
Bone Marrow
Brain
Breast
Spinal Cord
Cervix
Chest Wall
Colon
Endometrium
Esophagus
Eye
Fallopian Tube
Fibroadipose Tissue
Gall Bladder
Kidney
Larynx
Liver
Lung
Lymph Node
Nasal Cavity
Oral Cavity
Ovary
Pancreas
Parathyroid
Penis
Peripheral Nervous System
Peritoneum
Pharynx
Pituitary
Placenta
Pleura
Prostate
Retroperitoneum
Salivary Gland
Seminal Vesicle
Skeletal Muscle
Skin
Small Intestine
Soft Tissue
Spleen
Stomach
Testis
Thymus
Thyroid
Tonsil
Unknown
Ureter
Uterus
Vagina
Rectum
Cartilage
Blood Vessel
Buccal Swab
Heart
Trachea
Salivary Duct
Spermatic Cord
Vulva
Brain, Infratentorial
Brain, Supratentorial
Gastroesophageal Junction
Sellar
Suprasellar
Peritoneal fluid
Pleural Fluid
Tongue
Tumor Types
Acinar Cell Carcinoma
Acinic Cell Carcinoma
Adenocarcinoma
Adenoid Cystic Carcinoma
Adenosarcoma
Ameloblastic Tumor
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Angiomatoid Fibrous Histiocytoma
Angiomatosis
Angiomyolipoma
Angiosarcoma
Astrocytoma, Anaplastic
Basal Cell Carcinoma
Burkitt Lymphoma
Carcinoid Tumor
Carcinoma
Carcinosarcoma
Cholangiocarcinoma
Chondrosarcoma
Chordoma
Choriocarcinoma
Chromophobe Renal Cell Carcinoma
Chronic Lymphocytic Leukemia
Classical Hodgkin Lymphoma
Clear Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Craniopharyngioma
Dermatofibrosarcoma
Desmoplastic Small Round Cell Tumor
Diffuse Large B Cell Lymphoma
Ductal Carcinoma
Ependymoma
Ewing Sarcoma
Fibromatosis
Follicular Carcinoma
Follicular Lymphoma
Gastrointestinal Stromal Tumor
Germ Cell Tumor
Giant Cell Tumor
Glioblastoma
Glomus Tumor
Granular Cell Tumor
Hairy Cell Leukemia
Hemangioendothelioma
Hepatocellular Carcinoma
Invasive Ductal Carcinoma
Kaposi Sarcoma
Leiomyoma
Leiomyosarcoma
Lipoma
Liposarcoma
Lobular Carcinoma
Lymphoplasmacytic Lymphoma
Malignant Mullerian Mixed Tumor
Mantle Cell Lymphoma
Marginal Zone B Cell Lymphoma
Medullary Carcinoma
Medulloblastoma
Melanoma
Meningioma
Merkel Cell Carcinoma
Mesothelioma
Mucinous Adenocarcinoma
Mucinous Tumors of Ovary
Mucoepidermoid Carcinoma
Myxofibrosarcoma
Nasopharyngeal Carcinoma
Neuroblastoma
Neuroendocrine Carcinoma
Neuroendocrine Neoplasm
NK Cell Lymphoproliferative Disorder
NLPHL
Non-Small Cell Lung Carcinoma
Oligodendroglioma
Osteosarcoma
Papillary Carcinoma
Papillary Renal Cell Carcinoma
Peripheral T Cell Lymphoma
Pheochromocytoma
Plasma Cell Disorder
Post-Transplant Lymphoproliferative Disorder
Primitive Neuroectodermal Tumor
Renal Cell Carcinoma
Reninoma
Retinoblastoma
Rhabdomyosarcoma
Sarcoma
Schwannoma
Serous Carcinoma
Sex Cord Stromal Tumor
Small Cell Carcinoma
Solid Pseudopapillary Tumor of Pancreas
Spindle Cell Neoplasm
Squamous Cell Carcinoma
T Cell Lymphoproliferative Disorder
T-Cell LGL Leukemia
Thymic Carcinoma
Thymoma
Urothelial Carcinoma
Tumors of Peripheral Nerves
Unknown
Wilms Tumor
Ependymoma, Anaplastic
Astrocytoma, Pilocytic
Ganglioglioma
Neuroepithelial Neoplasm, NOS
Pleomorphic Carcinoma
Solitary Fibrous Tumor
Neuroepithelial neoplasm, high grade
Astrocytoma, NOS
Astrocytoma, Diffusely Infiltrating
Diffuse Midline Glioma
Infiltrating Glioma, NOS
Intraductal Papillary Mucinous Neoplasm (IPMN)
Lymphadenopathy
Lymphocytosis, Symptomatic
Monoclonal Gammopathy
Mucinous or Serous Cystic Neoplasms of Pancreas
Mycosis Fungoides, Unspecified Site
Oligodendroglioma, Anaplastic
Pleomorphic Xanthoastrocytoma
Rash and Other Nonspecific Skin Eruption
Hurthle Cell Carcinoma
High Grade Glioma
Undifferentiated Sarcoma
Glioma
Interpretation

This gene is a known cancer gene.

Last updated: 2019-08-28 14:53:58 UTC
Read More
Tier 2
NOTCH1
Variants
NOTCH1 any mutation
Primary Sites
Adrenal Gland
Anus
Ampulla (Pancreaticobiliary Duct)
Appendix
Bladder
Blood
Bone
Bone Marrow
Brain
Breast
Spinal Cord
Cervix
Chest Wall
Colon
Endometrium
Esophagus
Eye
Fallopian Tube
Fibroadipose Tissue
Gall Bladder
Kidney
Larynx
Liver
Lung
Lymph Node
Nasal Cavity
Oral Cavity
Ovary
Pancreas
Parathyroid
Penis
Peripheral Nervous System
Peritoneum
Pharynx
Pituitary
Placenta
Pleura
Prostate
Retroperitoneum
Salivary Gland
Seminal Vesicle
Skeletal Muscle
Skin
Small Intestine
Soft Tissue
Spleen
Stomach
Testis
Thymus
Thyroid
Tonsil
Unknown
Ureter
Uterus
Vagina
Rectum
Cartilage
Blood Vessel
Buccal Swab
Heart
Trachea
Salivary Duct
Spermatic Cord
Vulva
Brain, Infratentorial
Brain, Supratentorial
Gastroesophageal Junction
Sellar
Suprasellar
Peritoneal fluid
Pleural Fluid
Tongue
Tumor Types
Acinar Cell Carcinoma
Acinic Cell Carcinoma
Adenocarcinoma
Adenoid Cystic Carcinoma
Adenosarcoma
Ameloblastic Tumor
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Angiomatoid Fibrous Histiocytoma
Angiomatosis
Angiomyolipoma
Angiosarcoma
Astrocytoma, Anaplastic
Basal Cell Carcinoma
Burkitt Lymphoma
Carcinoid Tumor
Carcinoma
Carcinosarcoma
Cholangiocarcinoma
Chondrosarcoma
Chordoma
Choriocarcinoma
Chromophobe Renal Cell Carcinoma
Chronic Lymphocytic Leukemia
Classical Hodgkin Lymphoma
Clear Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Craniopharyngioma
Dermatofibrosarcoma
Desmoplastic Small Round Cell Tumor
Diffuse Large B Cell Lymphoma
Ductal Carcinoma
Ependymoma
Ewing Sarcoma
Fibromatosis
Follicular Carcinoma
Follicular Lymphoma
Gastrointestinal Stromal Tumor
Germ Cell Tumor
Giant Cell Tumor
Glioblastoma
Glomus Tumor
Granular Cell Tumor
Hairy Cell Leukemia
Hemangioendothelioma
Hepatocellular Carcinoma
Invasive Ductal Carcinoma
Kaposi Sarcoma
Leiomyoma
Leiomyosarcoma
Lipoma
Liposarcoma
Lobular Carcinoma
Lymphoplasmacytic Lymphoma
Malignant Mullerian Mixed Tumor
Mantle Cell Lymphoma
Marginal Zone B Cell Lymphoma
Medullary Carcinoma
Medulloblastoma
Melanoma
Meningioma
Merkel Cell Carcinoma
Mesothelioma
Mucinous Adenocarcinoma
Mucinous Tumors of Ovary
Mucoepidermoid Carcinoma
Myxofibrosarcoma
Nasopharyngeal Carcinoma
Neuroblastoma
Neuroendocrine Carcinoma
Neuroendocrine Neoplasm
NK Cell Lymphoproliferative Disorder
NLPHL
Non-Small Cell Lung Carcinoma
Oligodendroglioma
Osteosarcoma
Papillary Carcinoma
Papillary Renal Cell Carcinoma
Peripheral T Cell Lymphoma
Pheochromocytoma
Plasma Cell Disorder
Post-Transplant Lymphoproliferative Disorder
Primitive Neuroectodermal Tumor
Renal Cell Carcinoma
Reninoma
Retinoblastoma
Rhabdomyosarcoma
Sarcoma
Schwannoma
Serous Carcinoma
Sex Cord Stromal Tumor
Small Cell Carcinoma
Solid Pseudopapillary Tumor of Pancreas
Spindle Cell Neoplasm
Squamous Cell Carcinoma
T Cell Lymphoproliferative Disorder
T-Cell LGL Leukemia
Thymic Carcinoma
Thymoma
Urothelial Carcinoma
Tumors of Peripheral Nerves
Unknown
Wilms Tumor
Ependymoma, Anaplastic
Astrocytoma, Pilocytic
Ganglioglioma
Neuroepithelial Neoplasm, NOS
Pleomorphic Carcinoma
Solitary Fibrous Tumor
Neuroepithelial neoplasm, high grade
Astrocytoma, NOS
Astrocytoma, Diffusely Infiltrating
Diffuse Midline Glioma
Infiltrating Glioma, NOS
Intraductal Papillary Mucinous Neoplasm (IPMN)
Lymphadenopathy
Lymphocytosis, Symptomatic
Monoclonal Gammopathy
Mucinous or Serous Cystic Neoplasms of Pancreas
Mycosis Fungoides, Unspecified Site
Oligodendroglioma, Anaplastic
Pleomorphic Xanthoastrocytoma
Rash and Other Nonspecific Skin Eruption
Hurthle Cell Carcinoma
High Grade Glioma
Undifferentiated Sarcoma
Glioma
Interpretation

This gene is a known cancer gene.

Last updated: 2019-08-28 14:53:59 UTC
Read More
Tier 3
NOTCH1
Variants
NOTCH1 L2457V
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

NOTCH1 is a transmembrane receptor, which plays a role in cell fate determination, growth, and survival. Somatic activating mutations are common in T-cell lymphoblastic leukemia/lymphoma. Somatic alterations in NOTCH1 are very rare in colorectal adenocarcinoma and are identified in less than 1% of cases. NOTCH1 L2457V does not lie within any known functional domains of the NOTCH1 protein. L2457V has been identified in sequencing studies, but has not been biochemically characterized and therefore, its effect on protein function is unknown. The L2457V variant has been reported as a benign/likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/380420/). These results should be interpreted in the clinicopathologic context.

Last updated: 2018-03-15 01:02:47 UTC
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Tier 3
NOTCH1
Variants
NOTCH1 L2457V
Primary Sites
Breast
Tumor Types
Invasive Ductal Carcinoma
Interpretation

NOTCH1 is a transmembrane receptor, which plays a role in cell fate determination, growth, and survival. Somatic activating mutations are common in T-cell lymphoblastic leukemia/lymphoma. Somatic alterations in NOTCH1 are very rare in breast invasive ductal carcinoma and are identified in less than 1% of cases. NOTCH1 L2457V does not lie within any known functional domains of the NOTCH1 protein. L2457V has been identified in sequencing studies, but has not been biochemically characterized and therefore, its effect on protein function is unknown. The L2457V variant has been reported as a benign/likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/380420/). These results should be interpreted in the clinicopathologic context.

Last updated: 2018-03-30 16:10:01 UTC
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Tier 3
NOTCH1
Variants
NOTCH1 L2457V
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

NOTCH1 is a transmembrane receptor that plays a role in various cellular processes including cell fate determination, growth, and survival. NOTCH1 may be somatically mutated in a variety of cancers, and these mutations can be either gain- or loss-of-function mutations depending on the tumor type. Translocations and activating somatic mutations in NOTCH1 have been identified in T-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia. On the other hand, NOTCH1 loss-of-function somatic mutations are more common in solid tumors, namely squamous cell carcinomas, and occur as missense, frameshift or nonsense mutations. Somatic NOTCH1 mutations are rare in lung adenocarcinoma and are found in about 4% of cases. The NOTCH1 L2457V variant identified in this case has been reported as a benign germline finding in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/380420/). These results should be interpreted in the clinical context.

Last updated: 2018-06-13 19:00:04 UTC
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Tier 3
NOTCH1
Variants
NOTCH1 exon(s) 26-27 deletion
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

NOTCH1 is a transmembrane receptor, which plays a role in cell fate determination, growth, and survival. Notch signaling has been demonstrated to play a role in lung development and lung carcinogenesis. Notch activity is counteracted by NUMB. Gain-of-function mutations of NOTCH1 have been identified in approximately 10% of patients with non-small cell lung carcinoma (NSCLC). In addition, loss-of-function mutations in NUMB that allow for increased NOTCH1 activity have been observed in approximately 30% of NSCLC patients. Studies have observed that increased NOTCH1 expression is associated with a poor prognosis in patients with lung adenocarcinoma. The NOTCH1 intronic deletion variant (NM_017617:g.139397792_139397795del) is located nine base pairs downstream of exon 27. While the variant is located in close proximity to an exon-intron junction, a potential effect on gene splicing is unknown. These results should be interpreted in the clinical context.

Last updated: 2019-01-22 18:25:31 UTC
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Tier 3
NOTCH1
Variants
NOTCH1 L2457V
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Interpretation

NOTCH1 is a transmembrane receptor, which plays a role in cell fate determination, growth, and survival. Somatic alterations in NOTCH1 are very rare in thyroid carcinomas and are identified in less than 1% of cases. NOTCH1 L2457V does not lie within any known functional domains of the NOTCH1 protein. L2457V has been identified in sequencing studies, but has not been biochemically characterized and therefore, its effect on protein function is unknown. The L2457V variant has been reported as a benign/likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/380420/). These results should be interpreted in the clinicopathologic context.

Last updated: 2019-02-22 18:02:37 UTC
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