Gene Variant Detail

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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

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Transcript NM_020975
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 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38
NM_020630 chr10:g.43114502C>G c.1902C>G p.C634W RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Protein Effect Treatment Approaches
RET C634W gain of function RET Inhibitor
KDR pos RET C634W
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C634W thyroid gland 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 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 medullary 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 thyroid gland 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 gland medullary 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 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 medullary carcinoma sensitive BLU-667 Preclinical - Cell line xenograft Actionable In a preclinical study, BLU-667 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 thyroid gland 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 thyroid gland medullary carcinoma sensitive Selpercatinib Preclinical - Cell line xenograft Actionable In a preclinical study, thyroid medullary carcinoma cells harboring RET C634W were sensitive to treatment with Selpercatinib (LOXO-292), demonstrating decreased cell proliferation in culture and inhibition of tumor growth in cell line xenograft models (PMID: 29912274). 29912274
RET C634W thyroid gland medullary 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 thyroid gland medullary 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 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 gland medullary 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
KDR pos RET C634W thyroid gland medullary carcinoma predicted - sensitive Motesanib Preclinical - Cell line xenograft Actionable In a preclinical study, Motesanib (AMG 706) inhibited KDR (VEGFR2) phosphorylation, but had minimal activity against RET in a medullary thyroid carcinoma (MTC) cell line harboring RET C634W in culture, however, inhibited both RET and KDR (VEGFR2) phosphorylation and decreased tumor angiogenesis and growth in MTC cell line xenograft models with RET C634W (PMID: 21422803). 21422803