RET C634R
Gene Variant Detail

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Gene RET
Variant C634R
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET C634R lies within the extracellular domain of the Ret protein (UniProt.org). C634R results in autophosphorylation of Ret, and is transforming in cultured cells (PMID: 9242375, PMID: 10679286).
Associated Drug Resistance
Category Variants Paths

RET mutant RET act mut RET C634R

RET mutant RET C634X RET C634R

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Transcript NM_020975.6
gDNA chr10:g.43114500T>C
cDNA c.1900T>C
Protein p.C634R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020630.5 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_020975 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_020630 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_001406783.1 chr10:g.43123795T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_001406786.1 chr10:g.43123795T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43114500T>C c.1900T>C p.C634R RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C634R Advanced Solid Tumor sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET kinase activity and proliferation in transformed cells expressing RET C634R in culture (PMID: 16507829). 16507829
RET C634R Advanced Solid Tumor sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of cells expressing RET C634R in culture (PMID: 17664273). 17664273
RET C634R Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed human cell lines expressing RET C634R demonstrated sensitivity to Iclusig (ponatinib) (PMID: 23811235). 23811235
RET C634R Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited RET phosphorylation and decreased growth of transformed cells expressing RET C634R in culture (PMID: 15184865). 15184865
RET C634R Advanced Solid Tumor sensitive Vandetanib Preclinical - Cell culture Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET C634R in culture (PMID: 37535881). 37535881
RET C634R Advanced Solid Tumor sensitive Pz-1 Preclinical - Cell line xenograft Actionable In a preclinical study, Pz-1 inhibited Ret signaling in transformed cells over expressing RET C634R and inhibited tumor growth in cell line xenografts models (PMID: 26126987). 26126987
RET C634R Advanced Solid Tumor sensitive Pz-1 Preclinical - Cell culture Actionable In a preclinical study, Pz-1 treatment inhibited Ret phosphorylation and growth of transformed cells expressing RET C634R in culture (PMID: 34373541). 34373541
RET C634R medullary thyroid carcinoma predicted - sensitive Sorafenib Case Reports/Case Series Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in a partial response in 1 and stable disease in another patient with medullary thyroid carcinoma harboring RET C634R (PMID: 20368568; NCT00390325). 20368568
RET C634R Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET C634R in culture (PMID: 37535881). 37535881
RET C634R Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling and viability in transformed cells expressing RET C634R in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET C634R Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and viability in transformed cells expressing RET C634R in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET C634R malignant pheochromocytoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in stable disease lasting 9.4 months in a patient with metastatic pheochromocytoma harboring germline RET C634R and resulted in a partial response with treatment lasting 28.4 months in a second patient with metastatic pheochromocytoma harboring germline RET C634R (PMID: 38661071; NCT03157128). 38661071
RET C634R medullary thyroid carcinoma sensitive Selpercatinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55, 5 complete and 33 partial responses) in previously treated adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations as detected by an approved test, including RET C634R; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). detail... 32846061 detail...