MET exon 14 skipping mutation

aka METex14, MET exon 14 skipping, MET ex14, METΔex14, MET exon 14 alteration, MET splice site mutation

MET exon 14 skipping is a splice-site change that lets the MET receptor escape degradation and keep signalling. It is found in 3 to 4 percent of lung cancers and is treated with capmatinib or tepotinib.

Mutations at the exon 14 splice acceptor or donor sites, or in the Y1003 juxtamembrane region, cause the exon to be skipped, removing the CBL binding site. They are detected by DNA sequencing (with splice-site coverage) or, more sensitively, RNA sequencing of tissue or plasma. Capmatinib (Tabrecta, 2020) is labelled for metastatic NSCLC with a mutation that leads to MET exon 14 skipping as detected by an FDA-approved test, and tepotinib (Tepmetko, 2021) for NSCLC harbouring MET exon 14 skipping alterations; FoundationOne CDx and Liquid CDx are the companion diagnostics for both.

Part ofMET· METOther readoutsc-Met protein overexpression MET amplification All readouts

MET: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.

Sequencing 2 approval thresholds

What it means for a patient

A MET exon 14 skipping result means capmatinib or tepotinib, both tablets, are on label for advanced lung cancer. These tumours are common in older patients and respond less well to immunotherapy alone, so the MET tablet is usually chosen first or after one line of chemotherapy.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

A single nucleotide variant or indel at the MET exon 14 splice sites or within exon 14 that leads to exon 14 skipping, by DNA or RNA sequencing of tissue or plasma.

“MET single nucleotide variants and indels that lead to MET exon 14 skipping”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
MET exon 14 skipping	Capmatinib	Non-small-cell lung cancer	FDA	label
MET exon 14 skipping	Tepotinib	Non-small-cell lung cancer	FDA	label

Drugs whose label names it

Capmatinib Tepotinib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
FoundationOne CDx	Foundation Medicine	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Capmatinib	P170019/S011 (05/06/2020)
FoundationOne Liquid CDx	Foundation Medicine	Non-Small Cell Lung Cancer (NSCLC) - Plasma	Capmatinib	P190032/S001 (07/15/2021)
FoundationOne CDx	Foundation Medicine	Non-small cell lung cancer (NSCLC) - Tissue	Tepotinib	P170019/S067 (05/12/2026)

Tests that measure it

FoundationOne CDx FoundationOne Liquid CDx Tempus xT and xT CDx FoundationOne CDx FoundationOne Liquid CDx Caris MI Profile Guardant360 CDx Illumina TruSight Oncology Comprehensive

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.