# MET exon 14 skipping mutation

Source: https://onco.cc/terms/met-exon-14-skipping/  
OnCo record `met-exon-14-skipping` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A splice-site mutation that makes cells skip exon 14 of the MET gene removes the receptor's off switch, so MET piles up on the cell surface; found in about 3 percent of lung adenocarcinomas, typically in older smokers or never-smokers, it is targeted by the pills capmatinib, tepotinib and savolitinib.

## Summary

What is measured: a mutation at the splice sites flanking exon 14 of MET that deletes the juxtamembrane domain containing the Y1003 degradation signal. How: RNA-based next-generation sequencing is preferred because it detects the skipped transcript directly; DNA panels must cover the intronic splice regions and still miss 10 to 20 percent because the breakpoints vary; plasma cell-free DNA can detect it. Related tests: FISH or sequencing copy number for MET amplification (high-level gain, a MET to CEP7 ratio of 5 or more or ten copies or more, is more likely to respond) and c-Met immunohistochemistry for overexpression (3+ in half or more of cells selects telisotuzumab vedotin, not the kinase inhibitors). Frequency: 3 to 4 percent of non-small-cell lung cancers, 20 to 30 percent of pulmonary sarcomatoid carcinomas, and papillary renal cell carcinoma. What a positive result changes: capmatinib (GEOMETRY mono-1, response rate 68 percent first line), tepotinib (VISION) or savolitinib (China; and with osimertinib for MET-amplified resistance in EGFR-mutant disease) replace chemotherapy and immunotherapy, which works poorly here despite high PD-L1; resistance comes through MET D1228 and Y1230 mutations or KRAS and other bypass lesions; telisotuzumab vedotin serves c-Met-overexpressing EGFR wild-type nonsquamous disease. Where it matters: MET-altered NSCLC, NSCLC and papillary RCC.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: MET exon 14; METex14; MET ex14; MET exon 14 skipping; MET splice-site mutation; METex14 skipping alteration; c-Met immunohistochemistry; c-Met IHC; MET overexpression; MET copy number; MET-altered

## Connected records

- targets: [MET](https://onco.cc/targets/met/)
- terms: [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/), [On-target resistance mutations (gatekeeper, solvent-front, compound)](https://onco.cc/terms/gatekeeper-mutation/)
- drugs: [Capmatinib](https://onco.cc/drugs/capmatinib/), [Crizotinib](https://onco.cc/drugs/crizotinib/), [Savolitinib](https://onco.cc/drugs/savolitinib/), [Telisotuzumab vedotin](https://onco.cc/drugs/telisotuzumab-vedotin/), [Tepotinib](https://onco.cc/drugs/tepotinib/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- cancers: [MET exon 14 and MET-amplified non-small-cell lung cancer](https://onco.cc/cancers/met-altered-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Papillary renal cell carcinoma](https://onco.cc/cancers/papillary-rcc/)

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