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Gene | RET |
Variant | E632_L633del |
Impact List | deletion |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | RET E632_L633del results in the deletion of two amino acids in the cysteine-rich region of the Ret protein from amino acids 632 to 633 (PMID: 9879991). E632_L633del is transforming in cell culture (PMID: 9191060), and therefore, is predicted to lead to a gain of Ret protein function. |
Associated Drug Resistance | |
Category Variants Paths |
RET mutant RET act mut RET E632_L633del |
Transcript | NM_020975.6 |
gDNA | chr10:g.43114494_43114499delGAGCTG |
cDNA | c.1894_1899delGAGCTG |
Protein | p.E632_L633delEL |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001406773.1 | chr10:g.43118420_43118425delGTCCTG | c.1894_1899delGTCCTG | p.V632_L633delVL | RefSeq | GRCh38/hg38 |
NM_001406776.1 | chr10:g.43120094_43120099delACTTGG | c.1895_1900delACTTGG | p.D632_L633delDL | RefSeq | GRCh38/hg38 |
NM_001406791.1 | chr10:g.43126734_43126739delCATGCA | c.1894_1899delCATGCA | p.H632_A633delHA | RefSeq | GRCh38/hg38 |
NM_001406768.1 | chr10:g.43116605_43116610delCCTCGG | c.1894_1899delCCTCGG | p.P632_R633delPR | RefSeq | GRCh38/hg38 |
NM_020630.7 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406763.1 | chr10:g.43114630_43114635delGGAGGC | c.1895_1900delGGAGGC | p.R632_R633delRR | RefSeq | GRCh38/hg38 |
NM_001406769.1 | chr10:g.43118378_43118383delGCCTCC | c.1894_1899delGCCTCC | p.A632_S633delAS | RefSeq | GRCh38/hg38 |
NM_020975 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406744.1 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406782.1 | chr10:g.43122006_43122011delCAAAGT | c.1894_1899delCAAAGT | p.Q632_S633delQS | RefSeq | GRCh38/hg38 |
NM_001406790.1 | chr10:g.43126614_43126619delCTGATT | c.1894_1899delCTGATT | p.L632_I633delLI | RefSeq | GRCh38/hg38 |
NM_001406764.1 | chr10:g.43114623_43114628delACCTTC | c.1894_1899delACCTTC | p.T632_F633delTF | RefSeq | GRCh38/hg38 |
NM_001406788.1 | chr10:g.43126614_43126619delCTGATT | c.1894_1899delCTGATT | p.L632_I633delLI | RefSeq | GRCh38/hg38 |
NM_001355216.1 | chr10:g.43120129_43120134delCGGAAG | c.1894_1899delCGGAAG | p.R632_K633delRK | RefSeq | GRCh38/hg38 |
NM_001406786.1 | chr10:g.43123789_43123794delGACAAC | c.1894_1899delGACAAC | p.D632_N633delDN | RefSeq | GRCh38/hg38 |
NM_001406780.1 | chr10:g.43122006_43122011delCAAAGT | c.1894_1899delCAAAGT | p.Q632_S633delQS | RefSeq | GRCh38/hg38 |
NM_001406761.1 | chr10:g.43114623_43114628delACCTTC | c.1894_1899delACCTTC | p.T632_F633delTF | RefSeq | GRCh38/hg38 |
NM_001406789.1 | chr10:g.43126614_43126619delCTGATT | c.1894_1899delCTGATT | p.L632_I633delLI | RefSeq | GRCh38/hg38 |
NM_001406765.1 | chr10:g.43114630_43114635delGGAGGC | c.1895_1900delGGAGGC | p.R632_R633delRR | RefSeq | GRCh38/hg38 |
NM_001406777.1 | chr10:g.43120094_43120099delACTTGG | c.1895_1900delACTTGG | p.D632_L633delDL | RefSeq | GRCh38/hg38 |
NM_020630 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406759.1 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406781.1 | chr10:g.43122006_43122011delCAAAGT | c.1894_1899delCAAAGT | p.Q632_S633delQS | RefSeq | GRCh38/hg38 |
NM_020975.6 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406783.1 | chr10:g.43123789_43123794delGACAAC | c.1894_1899delGACAAC | p.D632_N633delDN | RefSeq | GRCh38/hg38 |
NM_020975.5 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406766.1 | chr10:g.43116629_43116634delAAAACT | c.1894_1899delAAAACT | p.K632_T633delKT | RefSeq | GRCh38/hg38 |
NM_001406774.1 | chr10:g.43119557_43119562delGCCAAA | c.1894_1899delGCCAAA | p.A632_K633delAK | RefSeq | GRCh38/hg38 |
NM_001406772.1 | chr10:g.43118378_43118383delGCCTCC | c.1894_1899delGCCTCC | p.A632_S633delAS | RefSeq | GRCh38/hg38 |
NM_001406767.1 | chr10:g.43116629_43116634delAAAACT | c.1894_1899delAAAACT | p.K632_T633delKT | RefSeq | GRCh38/hg38 |
NM_001406778.1 | chr10:g.43120094_43120099delACTTGG | c.1895_1900delACTTGG | p.D632_L633delDL | RefSeq | GRCh38/hg38 |
NM_001406785.1 | chr10:g.43123780_43123785delGAGAGG | c.1894_1899delGAGAGG | p.E632_R633delER | RefSeq | GRCh38/hg38 |
NM_001406779.1 | chr10:g.43122006_43122011delCAAAGT | c.1894_1899delCAAAGT | p.Q632_S633delQS | RefSeq | GRCh38/hg38 |
NM_001406787.1 | chr10:g.43123795_43123800delTGCAGC | c.1894_1899delTGCAGC | p.C632_S633delCS | RefSeq | GRCh38/hg38 |
NM_020630.5 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001355216.2 | chr10:g.43120129_43120134delCGGAAG | c.1894_1899delCGGAAG | p.R632_K633delRK | RefSeq | GRCh38/hg38 |
NM_001406771.1 | chr10:g.43118420_43118425delGTCCTG | c.1894_1899delGTCCTG | p.V632_L633delVL | RefSeq | GRCh38/hg38 |
NM_001406784.1 | chr10:g.43123753_43123758delAACCTT | c.1894_1899delAACCTT | p.N632_L633delNL | RefSeq | GRCh38/hg38 |
NM_001406775.1 | chr10:g.43120094_43120099delACTTGG | c.1895_1900delACTTGG | p.D632_L633delDL | RefSeq | GRCh38/hg38 |
NM_001406762.1 | chr10:g.43114623_43114628delACCTTC | c.1894_1899delACCTTC | p.T632_F633delTF | RefSeq | GRCh38/hg38 |
NM_001406760.1 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
NM_001406770.1 | chr10:g.43116629_43116634delAAAACT | c.1894_1899delAAAACT | p.K632_T633delKT | RefSeq | GRCh38/hg38 |
NM_001406743.1 | chr10:g.43114494_43114499delGAGCTG | c.1894_1899delGAGCTG | p.E632_L633delEL | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RET E632_L633del | Advanced Solid Tumor | conflicting | Pralsetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing RET E632_L633del was less sensitive to Gavreto (pralsetinib) than cells expressing wild-type RET in culture (PMID: 36416226). | 36416226 |
RET E632_L633del | Advanced Solid Tumor | conflicting | Pralsetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET E632_L633del in culture (PMID: 36166639). | 36166639 |
RET E632_L633del | medullary thyroid carcinoma | conflicting | Selpercatinib | Case Reports/Case Series | Actionable | In a clinical case study, Retevmo (selpercatinib) treatment resulted in limited activity in a patient with medullary thyroid carcinoma harboring RET E632_L633del, with a partial response achieved at cycle 9 but significant progressive disease observed at cycle 13 (PMID: 36416226; NCT03157128). | 36416226 |
RET E632_L633del | medullary thyroid carcinoma | conflicting | Selpercatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Retevmo (selpercatinib) resulted in a partial response in the target lesions and stable disease in the non-target lesions in a patient with sporadic medullary thyroid cancer harboring RET E632_L633del, and treatment continued for at least 17 months (PMID: 35616103; NCT03906331). | 35616103 |
RET E632_L633del | Advanced Solid Tumor | conflicting | Selpercatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing RET E632_L633del was less sensitive to Retevmo (selpercatinib) than cells expressing wild-type RET in culture (PMID: 36416226). | 36416226 |
RET E632_L633del | Advanced Solid Tumor | conflicting | Selpercatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET E632_L633del in culture (PMID: 36166639). | 36166639 |