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Gene | POLE |
Variant | V411L |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | POLE V411L lies within the exonuclease domain of the Pole protein (PMID: 29352080). V411L results in reduced Pole exonuclease activity in an in vitro assay (PMID: 25228659), and therefore, is predicted to lead to a loss of Pole protein function. |
Associated Drug Resistance | |
Category Variants Paths |
POLE mutant POLE inact mut POLE V411L |
Transcript | NM_006231.4 |
gDNA | chr12:g.132673703C>G |
cDNA | c.1231G>C |
Protein | p.V411L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011534799.2 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
XM_011534795.4 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
NM_006231.4 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
XM_011534800 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
XM_011534795.3 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
XM_011534795 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
NM_006231.3 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
NM_006231 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
XM_011534799 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
XM_011534799.3 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
XM_047429018.1 | chr12:g.132673703C>G | c.1231G>C | p.V411L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
POLE V411L | endometrial cancer | predicted - sensitive | Nivolumab | Case Reports/Case Series | Actionable | In a Phase II trial, Opdivo (nivolumab) resulted in a partial response in two patients with endometrial cancer harboring POLE V411L, along with high tumor mutational burden (PMID: 35398880; NCT03012581). | 35398880 |
POLE V411L | melanoma | sensitive | unspecified PD-1 antibody | Preclinical | Actionable | In a preclinical study, a murine anti-PD1 antibody inhibited tumor growth in a syngeneic mouse model of melanoma expressing POLE V411L (PMID: 35817971). | 35817971 |
POLE V411L | colorectal cancer | predicted - sensitive | Ipilimumab + Nivolumab | Case Reports/Case Series | Actionable | In a retrospective study, treatment with immune checkpoint inhibitors resulted in an overall response rate of 89% (22/29) and a disease control rate of 92% in metastatic colorectal cancer patients harboring pathogenic POLE/POLD1 variants, including a partial response in two patients harboring POLE V411L treated with the combination of Yervoy (ipilimumab) and Opdivo (nivolumab) (PMID: 38777726). | 38777726 |
POLE V411L | colorectal cancer | predicted - sensitive | Pembrolizumab | Case Reports/Case Series | Actionable | In a retrospective study, treatment with immune checkpoint inhibitors resulted in an overall response rate of 89% (22/29) and a disease control rate of 92% in metastatic colorectal cancer patients harboring pathogenic POLE/POLD1 variants, including a partial response in two patients harboring POLE V411L treated with Keytruda (pembrolizumab) (PMID: 38777726). | 38777726 |