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RET E632_L633del - Gene Variant Detail

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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

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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_001406787.1 chr10:g.43123795_43123800delTGCAGC c.1894_1899delTGCAGC p.C632_S633delCS RefSeq GRCh38/hg38
NM_001406769.1 chr10:g.43118378_43118383delGCCTCC c.1894_1899delGCCTCC p.A632_S633delAS RefSeq GRCh38/hg38
NM_001406779.1 chr10:g.43122006_43122011delCAAAGT c.1894_1899delCAAAGT p.Q632_S633delQS RefSeq GRCh38/hg38
NM_001406759.1 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_001406771.1 chr10:g.43118420_43118425delGTCCTG c.1894_1899delGTCCTG p.V632_L633delVL RefSeq GRCh38/hg38
NM_001406772.1 chr10:g.43118378_43118383delGCCTCC c.1894_1899delGCCTCC p.A632_S633delAS RefSeq GRCh38/hg38
NM_001406762.1 chr10:g.43114623_43114628delACCTTC c.1894_1899delACCTTC p.T632_F633delTF RefSeq GRCh38/hg38
NM_001406791.1 chr10:g.43126734_43126739delCATGCA c.1894_1899delCATGCA p.H632_A633delHA RefSeq GRCh38/hg38
NM_020630 chr10:g.43114494_43114499delGAGCTG c.1894_1899delGAGCTG p.E632_L633delEL RefSeq GRCh38/hg38
NM_001406760.1 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_001406766.1 chr10:g.43116629_43116634delAAAACT c.1894_1899delAAAACT p.K632_T633delKT RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43114494_43114499delGAGCTG c.1894_1899delGAGCTG p.E632_L633delEL RefSeq GRCh38/hg38
NM_001406778.1 chr10:g.43120094_43120099delACTTGG c.1895_1900delACTTGG p.D632_L633delDL RefSeq GRCh38/hg38
NM_001355216.2 chr10:g.43120129_43120134delCGGAAG c.1894_1899delCGGAAG p.R632_K633delRK RefSeq GRCh38/hg38
NM_001406782.1 chr10:g.43122006_43122011delCAAAGT c.1894_1899delCAAAGT p.Q632_S633delQS RefSeq GRCh38/hg38
NM_001406783.1 chr10:g.43123789_43123794delGACAAC c.1894_1899delGACAAC p.D632_N633delDN RefSeq GRCh38/hg38
NM_001406765.1 chr10:g.43114630_43114635delGGAGGC c.1895_1900delGGAGGC p.R632_R633delRR RefSeq GRCh38/hg38
NM_001406763.1 chr10:g.43114630_43114635delGGAGGC c.1895_1900delGGAGGC p.R632_R633delRR RefSeq GRCh38/hg38
NM_001406767.1 chr10:g.43116629_43116634delAAAACT c.1894_1899delAAAACT p.K632_T633delKT RefSeq GRCh38/hg38
NM_001406784.1 chr10:g.43123753_43123758delAACCTT c.1894_1899delAACCTT p.N632_L633delNL 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_001406764.1 chr10:g.43114623_43114628delACCTTC c.1894_1899delACCTTC p.T632_F633delTF RefSeq GRCh38/hg38
NM_001406786.1 chr10:g.43123789_43123794delGACAAC c.1894_1899delGACAAC p.D632_N633delDN RefSeq GRCh38/hg38
NM_001406789.1 chr10:g.43126614_43126619delCTGATT c.1894_1899delCTGATT p.L632_I633delLI RefSeq GRCh38/hg38
NM_001406785.1 chr10:g.43123780_43123785delGAGAGG c.1894_1899delGAGAGG p.E632_R633delER RefSeq GRCh38/hg38
NM_001406770.1 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_001406775.1 chr10:g.43120094_43120099delACTTGG c.1895_1900delACTTGG p.D632_L633delDL RefSeq GRCh38/hg38
NM_001406773.1 chr10:g.43118420_43118425delGTCCTG c.1894_1899delGTCCTG p.V632_L633delVL RefSeq GRCh38/hg38
NM_001406790.1 chr10:g.43126614_43126619delCTGATT c.1894_1899delCTGATT p.L632_I633delLI RefSeq GRCh38/hg38
NM_020975 chr10:g.43114494_43114499delGAGCTG c.1894_1899delGAGCTG p.E632_L633delEL RefSeq GRCh38/hg38
NM_001406768.1 chr10:g.43116605_43116610delCCTCGG c.1894_1899delCCTCGG p.P632_R633delPR RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43114494_43114499delGAGCTG c.1894_1899delGAGCTG p.E632_L633delEL RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43114494_43114499delGAGCTG c.1894_1899delGAGCTG p.E632_L633delEL RefSeq GRCh38/hg38
NM_001406776.1 chr10:g.43120094_43120099delACTTGG c.1895_1900delACTTGG p.D632_L633delDL RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43114494_43114499delGAGCTG c.1894_1899delGAGCTG p.E632_L633delEL RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43114494_43114499delGAGCTG c.1894_1899delGAGCTG p.E632_L633delEL RefSeq GRCh38/hg38
NM_001355216.1 chr10:g.43120129_43120134delCGGAAG c.1894_1899delCGGAAG p.R632_K633delRK RefSeq GRCh38/hg38
NM_001406788.1 chr10:g.43126614_43126619delCTGATT c.1894_1899delCTGATT p.L632_I633delLI RefSeq GRCh38/hg38
NM_001406777.1 chr10:g.43120094_43120099delACTTGG c.1895_1900delACTTGG p.D632_L633delDL RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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
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