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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 |
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_001406760.1 | 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_020630 | chr10:g.43114500T>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_020975.5 | 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 |
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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 | 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 | 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 |