Variant · Snv

RET M918T

CI-VAR-00002614Explore in graph →NP_065681.1:p.Met918ThrNM_020975.4:c.2753T>CClinVar 13919 CIViC 113 rs74799832

Curated evidence

Evidence by cancer (19 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–19 of 19 evidence items across 4 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Malignant Neoplasm4
RET M918T	(oncogenic)	Oncogenic	D	Supports Oncogenicity	4	accepted	EID11723 Recurrent somatic mutations within or near the RET kinase domain (T930K/M/P and D898_E901del) were identified in a large study of 37,056 East Asian cancer patients. After excluding RET mutations with … (full text at CIViC) PMID 32284345 · Zhao et al., 2020 · Open in CIViC	civic
RET M918T	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	accepted	EID12709 Two novel somatic interstitial in-frame deletions in RET, with unknown transformation potential, were identified in medullary thyroid carcinoma (MTC) tumor samples. One of these (RET E632_L633del) was… (full text at CIViC) PMID 9191060 · Ceccherini et al., 1997 · Open in CIViC	civic

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
13919	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts	2	Thyroid carcinoma, sporadic medullary; Pheochromocytoma; Multiple endocrine neoplasia type 2B; Multiple endocrine neoplasia, type 2; Multiple endocrine neoplasia type 2A; Medullary thyroid carcinoma; Hirschsprung disease, susceptibility to, 1; Familial medullary thyroid carcinoma; Hereditary cancer-predisposing syndrome; RET-related disorder; Inherited phaeochromocytoma and paraganglioma excluding NF1

Thyroid Gland Medullary Carcinoma13
RET M918T	(prognostic)	Prognostic	B	Supports Poor Outcome	2	accepted	EID78 In a study of 64 patients (48 kindreds), 62 had germline mutations at known hotspots in RET. Patients with RET M918T mutation were associated with MEN 2B subtype and developed larger and more aggressi… (full text at CIViC) PMID 9839497 · Egawa et al., 1998 · Open in CIViC	civic
RET M918T	(oncogenic)	Oncogenic	B	Supports Oncogenicity	3	accepted	EID12800 In a study of 100 patients with sporadic medullary thyroid carcinoma (MTC), RET gene exons 10-11 and 13-16 were analyzed with tumor and matched normal samples. A somatic RET mutation was identified in… (full text at CIViC) PMID 18073307 · Elisei et al., 2008 · Open in CIViC	civic
RET M918T	(predisposing)	Predisposing	C	Supports Predisposition	2	accepted	EID12711 A total of 56 metastatic medullary thyroid cancer cases (50 sporadic, 6 familial) were analyzed for RET mutations. A total of 7 cases were found to have a RET germline mutations however one case had a… (full text at CIViC) PMID 29515777 · Romei et al., 2018 · Open in CIViC	civic
RET M918T	Axitinib	Predictive	D	Supports Resistance	—	submitted	EID3696 In an in vitro study, a MZ-CRC-1 cell line expressing RET M918T mutation (endogenous) demonstrated resistance to axitinib treatment (IC50> 5uM). Resistance was determined by assessing cell viability. PMID 21470995 · Verbeek et al., 2011 · Open in CIViC	civic
RET M918T	Cabozantinib	Predictive	B	Supports Sensitivity Response	4	accepted	EID7710 In this retrospective analysis of a phase 3 trial of cabozantinib or placebo in 330 patients. Among those, 51.2% were RET mutation-positive (38.2% with RET M918T), 34.8% were RET mutation-unknown, and… (full text at CIViC) PMID 27525386 · Sherman et al., 2016 · Open in CIViC	civic
RET M918T	JAK2 Inhibitor AZD1480	Predictive	D	Supports Sensitivity Response	3	accepted	EID77 The use of AZD1480 on RET-mutated/rearranged cell lines in vitro led to strong repression of tyroid cancer cell growth. PMID 23056499 · Couto et al., 2012 · Open in CIViC	civic
RET M918T	Motesanib	Predictive	D	Supports Resistance	3	accepted	EID76 Medullary thyroid cancer cells with RET M918T mutation are insensitive to motesanib, compared to wild-type RET. PMID 21422803 · Coxon et al., 2012 · Open in CIViC	civic
RET M918T	Selpercatinib	Predictive	A	Supports Sensitivity Response	5	accepted	EID12598 The Phase 3 trial for the selective and brain-penetrant RET kinase inhibitor selpercatinib in Medullary Thyroid Cancer (MTC) LIBRETTO-531 (NCT04211337) consisted of 291 total patients. The patients … (full text at CIViC) PMID 37870969 · Hadoux et al., 2023 · Open in CIViC	civic
RET M918T	Selpercatinib	Predictive	C	Supports Sensitivity Response	4	rejected	EID11306 After progressing on 6 multi-kinase inhibitor (MKI) regimens (including sorafenib , vandetanib, cabozantinib, MGCD-516, RXDX-105, and vandetanib plus everolimus ), a metastatic medullary thyroid cance… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC	civic
RET M918T	Sorafenib	Predictive	B	Supports Sensitivity Response	3	accepted	EID1365 In a phase 2 clinical trial of sorafenib in patients with hereditary or sporadic advanced medullary thyroid cancer, 10 out of 12 patients genotyped in arm B (sporadic MTC) tested positive for RET muta… (full text at CIViC) PMID 20368568 · Lam et al., 2010 · Open in CIViC	civic
RET M918T AND RET G810S	Selpercatinib	Predictive	C	Supports Resistance	3	accepted	EID8196 In two out of three patients with MTC treated in a phase1/2 trial, the RET G810 mutation emerged in ctDNA together with an acquired resistance after initial response to selpercatinib. PMID 31988000 · Solomon et al., 2020 · Open in CIViC	civic
RET M918T AND RET V804M	Selpercatinib	Predictive	C	Supports Sensitivity Response	4	accepted	EID6950 After progressing on 6 multi-kinase inhibitor (MKI) regimens (including sorafenib , vandetanib, cabozantinib, MGCD-516, RXDX-105, and vandetanib plus everolimus ), a metastatic medullary thyroid cance… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC	civic
RET M918T AND RET V804M	Selpercatinib	Predictive	C	Supports Sensitivity Response	4	rejected	EID11307 After progressing on 6 multi-kinase inhibitor (MKI) regimens (including sorafenib , vandetanib, cabozantinib, MGCD-516, RXDX-105, and vandetanib plus everolimus ), a metastatic medullary thyroid cance… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC	civic