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Gene RET
Variant M918X
Impact List missense
Protein Effect unknown
Gene Variant Descriptions RET M918X indicates any Ret missense mutation that results in replacement of the methionine (M) at amino acid 918 by a different amino acid.
Associated Drug Resistance
Category Variants Paths

RET mutant RET M918X

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Transcript NM_020975.6
gDNA chr10:g.43121967_43121969
cDNA c.2752_2754
Protein p.M918
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020630 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_001406771.1 chr10:g.43128114_43128116 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_020975 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43121967_43121969 c.2752_2754 p.M918 RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was 44.9 mo in a patient harboring RET mutation, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
RET mutant medullary thyroid carcinoma sensitive Everolimus Phase II Actionable In a Phase II trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908; NCT01118065). 26294908
RET mutant Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of cancer cell lines harboring RET mutations in cultured and in cell line xenograft models (PMID: 23526464). 23526464
RET mutant medullary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant medullary thyroid carcinoma sensitive Selpercatinib FDA approved - Has Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55), with five complete and 33 partial responses, in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations who were previously treated, while patients who had not been previously treated demonstrated an ORR of 73% (64/88), with ten complete and 54 partial responses (PMID: 32846061; NCT03157128). detail... detail... 32846061
RET mutant medullary thyroid carcinoma sensitive Selpercatinib FDA approved - Has Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-121) that supported FDA approval, Retevmo (selpercatinib) treatment was safe in pediatric patients of 2 years or older with solid tumors (8 medullary thyroid cancer, 2 papillary thyroid cancer, 1 osteosarcoma) harboring RET fusion (n=2) or mutations (n=9), and resulted in unconfirmed partial responses in 4 patients, stable disease in 6 patients (two lasting >/=16 weeks) (JCO 39, 10009-10009(2021); NCT03899792). detail... detail... detail...
RET mutant medullary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...
RET mutant Advanced Solid Tumor predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated and demonstrated preliminary activity in patients with advanced solid tumors harboring mutations in RET, resulting in an objective response rate of 64%, with responses being observed in patients with non-small cell lung cancer, medullary thyroid cancer and pancreatic cancer (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...
RET mutant pheochromocytoma predicted - sensitive Sunitinib Case Reports/Case Series Actionable In a Phase II trial (SNIPP), a patient with pheochromocytoma harboring a germline RET mutation achieved a partial response to treatment with Sutent (sunitinib), and demonstrated a 64% reduction in tumor volume and remained on treatment for over 7 years (PMID: 31105270). 31105270
RET mutant cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited wild-type RET and RET mutations to prevent cell proliferation in cell culture (PMID: 17664273). 17664273
RET mutant medullary thyroid carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced or metastatic medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant medullary thyroid carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines (category 2B) for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...
RET mutant medullary thyroid carcinoma sensitive Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated and resulted in an overall response rate (ORR) of 60% (3/55) in patients with advanced or metastatic medullary thyroid cancer harboring RET mutations who received prior treatments, ORR was 60% (32/53) in patients with prior therapies and 71% (15/21) in treatment-naive patients (PMID: 34118198; NCT03037385). 34118198
RET mutant medullary thyroid carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (60 vs 20 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET mutations (PMID: 27525386). 27525386
RET mutant lung non-small cell carcinoma predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated in non-small cell lung cancer (NSCLC) patients harboring RET mutations, and resulted in an objective response rate (ORR) of 63% (20/32, 1 complete response (CR)) and disease control rate (DCR) of 91% in pretreated patients, and an ORR of 76% (19/25, 1 CR) and DCR of 92% with median duration of response not reached in treatment-naive patients, and an overall CNS DCR of 100% (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...
RET mutant colorectal cancer sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235