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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
Category Variants Paths

RET mutant RET M918X RET M918T

RET mutant RET act mut RET M918T

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Transcript NM_020975.6
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_020630.5 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
NM_001406759.1 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_020975 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43121968T>C c.2753T>C p.M918T RefSeq GRCh38/hg38
NM_001406771.1 chr10:g.43128115T>C c.2753T>C p.M918T RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 V804M RET M918T 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
RET V804M RET M918T thyroid gland medullary carcinoma predicted - 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 Retevmo (selpercatinib), 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 V804M RET M918T Advanced Solid Tumor predicted - sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited cell growth and Ret phosphorylation in transformed cells expressing RET V804M and M918T in culture (PMID: 33161056). 33161056
RET V804M RET G810S RET L881V RET M918T thyroid gland medullary carcinoma predicted - resistant Selpercatinib Case Reports/Case Series Actionable In a clinical case study, a patient with hereditary medullary thyroid carcinoma harboring germline RET M918T demonstrated disease progression following an initial response to Retevmo (selpercatinib), and ctDNA sequencing revealed a decrease in RET L881V, but an increase in RET V804M and RET G810S (PMID: 31988000). 31988000
RET V804M RET G810C RET M918T Advanced Solid Tumor resistant Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing RET V804M, G810C, and M918T were resistant to Retevmo (selpercatinib) treatment in culture (PMID: 33161056). 33161056
RET V804M RET G810S RET M918T Advanced Solid Tumor resistant Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing RET V804M, G810S, and M918T were resistant to Retevmo (selpercatinib) treatment in culture (PMID: 33161056). 33161056
RET V804M RET Y806C RET M918T Advanced Solid Tumor predicted - resistant Selpercatinib Preclinical - Biochemical Actionable In a preclinical study, transformed human cells expressing RET M918T, V804M, and Y806C in cis were resistant to Retevmo (selpercatinib) in culture (PMID: 35304457). 35304457
RET G810S RET M918T Advanced Solid Tumor predicted - sensitive TY-1091 Preclinical - Biochemical Actionable In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET G810S and M918T in culture (Cancer Res (2023) 83 (7_Supplement): 3419). detail...