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Gene RET
Variant C634W
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET C634W lies within the extracellular domain of the Ret protein (UniProt.org). C634W results in ligand independent dimerization and constitutive activation of Ret, and is transforming in culture (PMID: 10918602, PMID: 9230192).
Associated Drug Resistance
Category Variants Paths

RET mutant RET act mut RET C634W

RET mutant RET C634X RET C634W

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Transcript NM_020975.6
gDNA chr10:g.43114502C>G
cDNA c.1902C>G
Protein p.C634W
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020975.6 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_001406783.1 chr10:g.43123797C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_020630 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_001406786.1 chr10:g.43123797C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_020975 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C634W thyroid gland carcinoma sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of thyroid carcinoma cells harboring a RET C634W mutation in culture (PMID: 17664273). 17664273
RET C634W thyroid gland carcinoma sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET signaling and decreased growth of thyroid carcinoma cells harboring a RET C634W mutation in culture and in cell line xenograft models (PMID: 23526464). 23526464
RET C634W thyroid gland carcinoma sensitive Cabozantinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cometriq (cabozantinib) inhibited phosphorylation of RET C634W and decreased tumor growth in xenograft models of a human thyroid carcinoma cell line harboring RET C634W mutation (PMID: 23705946). 23705946
RET C634W thyroid cancer sensitive Lenvatinib Preclinical Actionable In a preclinical study, Lenvima (lenvatinib) inhibited RET phosphorylation and signaling in thyroid cancer cells expressing RET C634W (PMID: 25295214). 25295214
RET C634W medullary thyroid carcinoma sensitive Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and inhibited tumor growth in cell line xenograft models of medullary thyroid carcinoma harboring RET C634W (PMID: 16507829). 16507829
RET C634W medullary thyroid carcinoma sensitive XMD15-44 Preclinical Actionable In a preclinical study, XMD15-44 inhibited RET phosphorylation and downstream signaling and reduced proliferation of medullary thyroid carcinoma cells harboring RET C634W in culture (PMID: 26046350). 26046350
RET C634W medullary thyroid carcinoma sensitive ALW-II-41-27 Preclinical - Cell culture Actionable In a preclinical study, ALW-II-41-27 inhibited RET phosphorylation and downstream signaling and reduced proliferation of medullary thyroid carcinoma cells harboring RET C634W in culture (PMID: 26046350). 26046350
RET C634W medullary thyroid carcinoma sensitive HG-6-63-01 Preclinical Actionable In a preclinical study, HG-6-63-01 inhibited RET phosphorylation and downstream signaling and reduced proliferation of medullary thyroid carcinoma cells harboring RET C634W in culture (PMID: 26046350). 26046350
RET C634W thyroid cancer sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of thyroid cancer cells harboring RET C634W in culture (PMID: 21170960). 21170960
RET C634W thyroid cancer sensitive AZD1480 Preclinical - Cell culture Actionable In a preclinical study, AZD1480 reduced phosphorylation of RET and downstream effectors, and inhibited growth and increased apoptosis of a thyroid cancer cell line harboring RET C634W in culture (PMID: 23056499). 23056499
RET C634W medullary thyroid carcinoma sensitive RXDX-105 Preclinical - Cell culture Actionable In a preclinical study, RXDX-105 (CEP-32496) reduced phosphorylation of RET and downstream signaling and inhibited proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture (PMID: 28011461). 28011461
RET C634W medullary thyroid carcinoma sensitive Pralsetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture, and inhibited tumor growth in xenograft models (PMID: 29657135). detail... 29657135
RET C634W medullary thyroid carcinoma sensitive Selpercatinib Preclinical - Cell line xenograft Actionable In a preclinical study, thyroid medullary carcinoma cells harboring RET C634W were sensitive to treatment with Retevmo (selpercatinib), demonstrating decreased cell proliferation in culture and inhibition of tumor growth in cell line xenograft models (PMID: 29912274). 29912274
RET C634W medullary thyroid carcinoma sensitive Pz-1 Preclinical - Cell line xenograft Actionable In a preclinical study, Pz-1 treatment inhibited downstream signaling and cell growth of a medullary thyroid carcinoma cell line harboring RET C634W in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34373541). 34373541
RET C634W medullary thyroid carcinoma sensitive SYHA1815 Preclinical - Cell line xenograft Actionable In a preclinical study, SYHA1815 treatment inhibited RET signaling and proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture, and induced tumor regression in a cell line xenograft model (PMID: 34518294). 34518294
RET C634W thyroid cancer predicted - sensitive APS03118 Preclinical - Cell line xenograft Actionable In a preclinical study, APS03118 treatment inhibited proliferation of a thyroid cancer cell line harboring RET C634W in culture and inhibited tumor growth in a xenograft model (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET C634W thyroid cancer predicted - sensitive TY-1091 Preclinical - Cell line xenograft Actionable In a preclinical study, TY-1091 inhibited proliferation in a thyroid cancer cell line harboring RET C634W in culture and inhibited tumor growth in a cell line xenograft model (Cancer Res (2023) 83 (7_Supplement): 3419). detail...
RET C634W medullary thyroid carcinoma sensitive Vepafestinib Preclinical - Cell culture Actionable In a preclinical study, Vepafestinib (TAS0953/HM06) inhibited proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture (PMID: 37743366). 37743366
RET C634W medullary thyroid carcinoma sensitive MitoQ + Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Retevmo (selpercatinib) and MitoQ synergistically inhibited viability of a medullary thyroid cancer cell line harboring RET C634W in culture (PMID: 38378752). 38378752
RET C634W Advanced Solid Tumor sensitive SY-5007 Preclinical - Cell culture Actionable In a preclinical study, SY-5007 inhibited proliferation in cells expressing RET C634W in culture (PMID: 39489747). 39489747