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.

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.

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.

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.