Gene Variant Detail

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Gene RB1
Variant E268*
Impact List nonsense
Protein Effect loss of function - predicted
Gene Variant Descriptions RB1 E268* results in a premature truncation of the Rb1 protein within domain A at amino acid 268 of 928 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), E268* is predicted to lead to a loss of Rb1 protein function.
Associated Drug Resistance

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Transcript NM_000321
gDNA chr13:g.48362898G>T
cDNA c.802G>T
Protein p.E268*
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000321 chr13:g.48362898G>T c.802G>T p.E268* RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RB1 I101fs RB1 E268* RB1 V654fs RB1 T738_R775del Her2-receptor negative breast cancer predicted - resistant Fulvestrant + Palbociclib Case Reports/Case Series Actionable In a clinical case study, RB1 mutations including E268*, I101fs, T738_R775del, and V654fs were identified in the circulating tumor DNA of a patient with estrogen receptor positive, progesterone receptor positive, and Erbb2 (Her2)-negative, invasive ductal carcinoma at the time of disease progression after 8 months of Ibrance (palbociclib) and Faslodex (fulvestrant) combination treatment (PMID: 29236940). 29236940
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RB1 inact mut glioblastoma multiforme resistant Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, Ibrance (palbociclib) failed to inhibit growth of RB1-deficient glioblastoma cell lines in culture and in intracranial cell line xenograft models (PMID: 20354191). 20354191
RB1 inact mut retinoblastoma sensitive Nutlin-3a Preclinical Actionable In a preclinical study, Nutlin-3a induced p53 pathway signaling in MDMX mouse models with retinoblastoma and 69% (70/102) of the eyes harvested from the mouse models demonstrated complete response or stable disease after 18 weeks of therapy (PMID: 21515735). 21515735
RB1 inact mut retinoblastoma sensitive BAY 61-3606 Preclinical Actionable In a preclinical study, a retinoblastoma cell line was sensitive to BAY 61-3606 in cell culture and in xenograft models, demonstrating increased apoptosis (PMID: 22237022). 22237022
RB1 inact mut retinoblastoma sensitive Fostamatinib Preclinical Actionable In a preclinical study, retinoblastoma cell lines demonstrated sensitivity to Fostamatinib resulting in cell death (PMID: 22237022). 22237022
RB1 mutant osteosarcoma sensitive VCN-01 Preclinical - Cell line xenograft Actionable In a preclinical study, VCN-01 decreased viability of a human RB1-mutant primary osteosarcoma cell line in culture, and inhibited tumor growth and decreased lung metastases in xenograft models (PMID: 26603261). 26603261
RB1 mutant estrogen-receptor positive breast cancer predicted - resistant Palbociclib Phase III Actionable In a Phase III trial (PALOMA-3), acquired RB1 mutations were identified in patents with ER-positive, ERBB2 (HER2)-negative breast cancer at the end of treatment in the Faslodex (fulvestrant) plus Ibrance (palbociclib) but not the Faslodex (fulvestrant) plus placebo arm, suggesting a role in conferring resistance to Ibrance (palbociclib) (PMID: 30206110; NCT01942135). 30206110
Molecular Profile Protein Effect Treatment Approaches
RB1 E268* loss of function - predicted
RB1 I101fs RB1 E268* RB1 V654fs RB1 T738_R775del