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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 |
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 |
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 |