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Gene | POLD1 |
Variant | L474P |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | POLD1 L474P lies within the exonuclease domain of the Pold1 protein (PMID: 27093186). L474P has been associated with increased single-base substitution in patient cells (PMID: 34594041), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Dec 2024). |
Associated Drug Resistance | |
Category Variants Paths |
POLD1 mutant POLD1 L474P |
Transcript | NM_002691.4 |
gDNA | chr19:g.50406444T>C |
cDNA | c.1421T>C |
Protein | p.L474P |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002691.4 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_005259008.4 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
NM_001256849.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_017026882.3 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_011527038.2 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
NM_001308632.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_011527038.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
NM_001308632.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_047438946.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_047438947.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
NM_002691.3 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_017026882.2 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_005259008.5 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_047438950.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_017026881.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_047438948.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
XM_047438949.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
NM_001256849.1 | chr19:g.50406444T>C | c.1421T>C | p.L474P | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
POLD1 mutant | Advanced Solid Tumor | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). | 31415061 |
POLD1 mutant | Advanced Solid Tumor | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). | 31415061 |
POLD1 mutant | Advanced Solid Tumor | predicted - sensitive | unspecified CTLA4 antibody | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). | 31415061 |