Gene Variant Detail

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Gene RET
Variant M918T
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET M918T lies within the protein kinase domain of the Ret protein (Uniprot.org). M918T results in ligand-independent autophosphorylation of Ret and increased substrate binding, is transforming (PMID: 17108110), and confers drug resistance in the context of KIF5B-RET in culture (PMID: 29908090).
Associated Drug Resistance Y

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Transcript NM_020975
gDNA chr10:g.43121968T>C
cDNA c.2753T>C
Protein p.M918T
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020975 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_020630 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38

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  • 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 M918T gain of function RET Inhibitor
ATM L804fs ATM S978fs RET M918T
RET M918T RET V804M
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET M918T Advanced Solid Tumor sensitive ALW-II-41-27 Preclinical - Cell culture Actionable In a preclinical study, ALW-II-41-27 inhibited RET phosphorylation and downstream signaling, reduced proliferation of transformed cells expressing RET M918T in culture (PMID: 26046350). 26046350
RET M918T thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, and 4 of the 7 patients carried a RET M918T mutation (PMID: 26294908). 26294908
RET M918T 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 M918T in culture (PMID: 26046350). 26046350
RET M918T thyroid gland medullary carcinoma sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, thyroid medullary carcinoma cells harboring RET M918T were sensitive to treatment with Selpercatinib (LOXO-292) in culture, demonstrating decreased cell proliferation (PMID: 29912274). 29912274
RET M918T lung small cell carcinoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited growth of small cell lung carcinoma lines expressing RET M918T (PMID: 25122427). 25122427
RET M918T 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 thryoid carcinoma cells harboring RET M918T in culture (PMID: 26046350). 26046350
RET M918T lung small cell carcinoma sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited growth of small cell lung carcinoma lines expressing RET M918T (PMID: 25122427). 25122427
RET M918T thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) increased overall survival to 25.4 months in medullary thyroid carcinoma patients with RET M918T (J Clin Oncol 33, 2015, suppl; abstr 6012). detail...
RET M918T thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (61 vs 17 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET M918T (PMID: 27525386). 27525386
RET M918T thyroid gland medullary carcinoma 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 medullary thyroid cancer cell line harboring RET M918T in culture (PMID: 23056499). 23056499
RET M918T Advanced Solid Tumor sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased proliferation of cells expressing RET M918T in culture (PMID: 17664273). 17664273
RET M918T thyroid gland medullary carcinoma predicted - sensitive BLU-667 Phase I Actionable In a Phase I trial, a patient with sporadic medullary thryoid cancer harboring RET M918T demonstrated a partial response, with maximal tumor reduction of 47% following treatment with BLU-667 (PMID: 29657135; NCT03037385). 29657135
RET M918T thyroid gland carcinoma sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET signaling and decreased proliferation of thyroid carcinoma cells harboring a RET M918T mutation in culture (PMID: 23526464). 23526464
RET M918T thyroid gland medullary carcinoma predicted - sensitive Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in partial response in 10% (1/10) and stable disease in 90% (9/10) of patients with medullary thyroid carcinoma harboring RET M918T (PMID: 20368568). 20368568
RET M918T Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing RET M918T were sensitive to treatment with Selpercatinib (LOXO-292) in culture, demonstrating decreased cell proliferation (PMID: 29912274). 29912274
RET M918T Advanced Solid Tumor sensitive XMD15-44 Preclinical Actionable In a preclinical study, XMD15-44 inhibited RET phosphorylation and downstream signaling and reduced proliferation of transformed cells expressing RET M918T in culture (PMID: 26046350). 26046350
RET M918T Advanced Solid Tumor 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 transformed cells expressing RET M918T in culture (PMID: 26046350). 26046350
RET M918T Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation and transforming activity in cells expressing RET M918T in culture (PMID: 15184865). 15184865
RET M918T Advanced Solid Tumor predicted - sensitive Pz-1 Preclinical Actionable In a preclinical study, Pz-1 inhibited Ret phosphorylation in transformed cells expressing RET M918T (PMID: 26126987). 26126987
RET M918T Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited phosphorylation of Ret in transformed human cells expressing RET M918T in culture (PMID: 23526464). 23526464
RET M918T colorectal cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of colorectal cancer cells harboring a RET M918T mutation in culture (PMID: 17664273). 17664273
RET M918T 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 M918T in culture (PMID: 26046350). 26046350
ATM L804fs ATM S978fs RET M918T thyroid gland medullary carcinoma predicted - sensitive Everolimus + Vandetanib Case Reports/Case Series Actionable In a clinical case study, addition of Afinitor (everolimus) to Caprelsa (vandetanib) treatment resulted in significant tumor reduction in a medullary thyroid carcinoma patient harboring ATM L804fs*4, ATM S978fs*12, and RET M918T, that achieved prolonged stable disease on Caprelsa (vandetanib) treatment alone (PMID: 27683183). 27683183
RET M918T RET V804M thyroid gland medullary carcinoma sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, a patient with thyroid medullary cancer harboring RET M918T and RET V804M demonstrated an initial response to Selpercatinib (LOXO-292), which included a decrease in allelic fraction of RET M918T and RET V804M over 8 weeks and a radiographic response of nearly 54% post 6.9 months of treatment (PMID: 29912274; NCT03157128). 29912274
RET M918T RET V804M lung adenocarcinoma resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma initially treated with chemotherapy and immunotherapy was found to harbor KIF5B-RET, and was then treated with Alecensa (alectinib), which resulted in an intracranial response, but eventually led to further progression (PMID: 29912274; NCT03157128). 29912274
RET M918T RET V804M thyroid gland medullary carcinoma resistant Everolimus + Vandetanib Case Reports/Case Series Actionable In a clinical case study, a patient with thyroid medullary carcinoma harboring RET M918T progressed on multiple therapies, including Nexavar (sorafenib), Caprelsa (vandetanib), Cometriq (cabozantinib), MGCD-516 (sitravatinib), and RXDX-105 (CEP-32496), and upon progression with the combination therapy, Caprelsa (vandetanib) and Afinitor (everolimus), cell-free DNA testing revealed RET M918T and acquisition of a secondary drug resistant mutation, RET V804M (PMID: 29912274; NCT03157128). 29912274