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Gene | NOTCH1 |
Variant | S2467fs |
Impact List | frameshift |
Protein Effect | unknown |
Gene Variant Descriptions | NOTCH1 S2467fs results in a change in the amino acid sequence of the Notch1 protein beginning at aa 2467 of 2555, likely resulting in premature truncation of the functional protein (UniProt.org). S2467fs does not result in statistically significant increase of Notch1 signaling in a reporter assay (PMID: 27870570), but has not been fully characterized and therefore, its effect on Notch1 protein function is unknown (PubMed, Oct 2020). |
Associated Drug Resistance |
Transcript | NM_017617.4 |
gDNA | chr9:g.(136496340_136496341) |
cDNA | c.(7399_7398) |
Protein | p.S2467fs |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_017617 | chr9:g.136496344_136496345insTT | c.7394_7395insAA | p.S2467fs*11 | RefSeq | GRCh38/hg38 |
NM_017617.4 | chr9:g.(136496340_136496341) | c.(7399_7398) | p.S2467fs | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
NOTCH1 L1600Q NOTCH1 S2467fs | adenoid cystic carcinoma | predicted - sensitive | Brontictuzumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic adenoid cystic carcinoma harboring co-occurring NOTCH1 L1600Q and S2467fs achieved a partial response after 2 doses of Brontictuzumab (OMP-52M51), however, his disease progressed shortly after treatment discontinuation (PMID: 27870570). | 27870570 |
FBXW7 W606* NOTCH1 L1600Q NOTCH1 V1721G NOTCH1 S2467fs | adenoid cystic carcinoma | no benefit | Sunitinib | Case Reports/Case Series | Actionable | In a clinical case study, Sutent (sunitinib) treatment resulted in rapid disease progression in a patient with metastatic adenoid cystic carcinoma harboring co-occurring NOTCH1 L1600Q and S2467fs, and acquired FBXW7 W606* and NOTCH1 V1721G (PMID: 27870570). | 27870570 |
FBXW7 W606* NOTCH1 L1600Q NOTCH1 V1721G NOTCH1 S2467fs | adenoid cystic carcinoma | predicted - resistant | Brontictuzumab | Case Reports/Case Series | Actionable | In a clinical case study, FBXW7 W606* and NOTCH1 V1721G were identified at disease progression in a patient with metastatic adenoid cystic carcinoma harboring co-occurring NOTCH1 L1600Q and S2467fs who was treated with Brontictuzumab (OMP-52M51) (PMID: 27870570). | 27870570 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
NOTCH1 S2467fs | unknown | Gamma secretase inhibitor NOTCH Inhibitor (Pan) NOTCH1 Antibody NOTCH1 Inhibitor |
NOTCH1 L1600Q NOTCH1 S2467fs | ||
FBXW7 W606* NOTCH1 L1600Q NOTCH1 V1721G NOTCH1 S2467fs |