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Gene | MLH1 |
Variant | E71del |
Impact List | deletion |
Protein Effect | loss of function |
Gene Variant Descriptions | MLH1 E71del results in the deletion of an amino acid within the ATPase domain of the Mlh1 protein (PMID: 22753075) at amino acid 71. E71del confers a loss of function on the Mlh1 protein as demonstrated by reduced mismatch repair activity (MMR) in an in vitro assay and altered subcellular localization as compared to wild-type (PMID: 21120944). |
Associated Drug Resistance | |
Category Variants Paths |
MLH1 mutant MLH1 inact mut MLH1 E71del |
Transcript | NM_000249.4 |
gDNA | chr3:g.37000960_37000962delAGA |
cDNA | c.213_215delAGA |
Protein | p.E71delE |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001167617.2 | chr3:g.37008865_37008867delCCA | c.211_213delCCA | p.P71delP | RefSeq | GRCh38/hg38 |
NM_001354629.1 | chr3:g.37004404_37004406delTTG | c.211_213delTTG | p.L71delL | RefSeq | GRCh38/hg38 |
XM_047448154.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
XM_005265166 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
NM_001354627.2 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_000249.4 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001354626.2 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001258271.1 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001354628.2 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001354620.1 | chr3:g.37008865_37008867delCCA | c.211_213delCCA | p.P71delP | RefSeq | GRCh38/hg38 |
NM_001258274.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001167618.3 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354617.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354630.2 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
XM_017006449 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
NM_001167619.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354625.2 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001354622.1 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
NM_001167617 | chr3:g.37008865_37008867delCCA | c.211_213delCCA | p.P71delP | RefSeq | GRCh38/hg38 |
XM_005265161 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
XM_047448155.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001258274.3 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354617.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
XM_005265161.2 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001354625.1 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001354615.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
XM_017006450 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
XM_047448153.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
XM_005265164 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001258273 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001258271 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001258273.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354623.1 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
NM_001167619 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354630.1 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001354618.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354621.2 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
NM_001354616.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_000249.3 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001167617.3 | chr3:g.37008865_37008867delCCA | c.211_213delCCA | p.P71delP | RefSeq | GRCh38/hg38 |
NM_001354627.1 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001167618.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001167618 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354620.2 | chr3:g.37008865_37008867delCCA | c.211_213delCCA | p.P71delP | RefSeq | GRCh38/hg38 |
NM_001258273.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354615.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354619.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354624.2 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001354619.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354623.2 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
XM_011533727 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001258274 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001258271.2 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
XM_017006451 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001354629.2 | chr3:g.37004404_37004406delTTG | c.211_213delTTG | p.L71delL | RefSeq | GRCh38/hg38 |
NM_001354626.1 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001354616.2 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_001354621.1 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
NM_001354628.1 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
XM_005265161.3 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
XM_005265163 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
XM_017006450.2 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
NM_001167619.3 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
NM_000249 | chr3:g.37000960_37000962delAGA | c.213_215delAGA | p.E71delE | RefSeq | GRCh38/hg38 |
NM_001354624.1 | chr3:g.37025886_37025888delGAG | c.214_216delGAG | p.E72delE | RefSeq | GRCh38/hg38 |
NM_001354622.2 | chr3:g.37025832_37025834delGTC | c.211_213delGTC | p.V71delV | RefSeq | GRCh38/hg38 |
XM_047448152.1 | chr3:g.37004404_37004406delTTG | c.211_213delTTG | p.L71delL | RefSeq | GRCh38/hg38 |
NM_001354618.1 | chr3:g.37020359_37020361delCAT | c.211_213delCAT | p.H71delH | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MLH1 inact mut | colorectal cancer | not applicable | N/A | Preclinical | Emerging | In a preclinical study, MLH1 inactivation through hypermethylation was associated with high microsatellite instability (MSI-H) colorectal carcinoma by whole genome sequencing of tumor samples (PMID: 22810696), suggesting it may be a potential biomarker. | 22810696 |
MLH1 inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | FDA approved | Actionable | In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including MLH1, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). | 37285865 detail... |
MLH1 inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | Guideline | Actionable | Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic MLH1 mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). | detail... |
MLH1 mutant | rectum cancer | not applicable | N/A | Guideline | Risk Factor | Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing colorectal cancer (NCCN.org). | detail... |
MLH1 mutant | stomach cancer | not applicable | N/A | Guideline | Risk Factor | Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of early onset of gastric cancer (NCCN.org). | detail... |
MLH1 mutant | ovarian cancer | not applicable | N/A | Guideline | Risk Factor | Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of ovarian cancer (NCCN.org). | detail... |
MLH1 mutant | colon cancer | not applicable | N/A | Guideline | Risk Factor | Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing colon cancer (NCCN.org). | detail... |
MLH1 mutant | endometrial carcinoma | not applicable | N/A | Guideline | Risk Factor | Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of developing endometrial carcinoma (NCCN.org). | detail... |
MLH1 mutant | pancreatic cancer | not applicable | N/A | Guideline | Risk Factor | Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org). | detail... |
MLH1 mutant | small intestine adenocarcinoma | not applicable | N/A | Guideline | Risk Factor | Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing small bowel adenocarcinoma (NCCN.org). | detail... |