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Gene ROS1
Variant L2026M
Impact List missense
Protein Effect unknown
Gene Variant Descriptions ROS1 L2026M lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2026M has been demonstrated to confer resistance to ROS1 inhibitors in the context of a Ros1 fusion (PMID: 25351743, PMID: 32918045), and results in increased colony formation, cell migration, and ERK/AKT signaling in the context of a ROS1 fusion in culture (PMID: 38148635), but has not been individually characterized and therefore, its effect on Ros1 protein function is unknown.
Associated Drug Resistance Y
Category Variants Paths

ROS1 mutant ROS1 L2026M

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Transcript NM_002944.3
gDNA chr6:g.117317202G>T
cDNA c.6076C>A
Protein p.L2026M
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002944 chr6:g.117317202G>T c.6076C>A p.L2026M RefSeq GRCh38/hg38
XM_011536050.3 chr6:g.117317229G>T c.6076C>A p.L2026M RefSeq GRCh38/hg38
XM_011536050 chr6:g.117317229G>T c.6076C>A p.L2026M RefSeq GRCh38/hg38
NM_002944.3 chr6:g.117317202G>T c.6076C>A p.L2026M RefSeq GRCh38/hg38
NM_002944.2 chr6:g.117317202G>T c.6076C>A p.L2026M RefSeq GRCh38/hg38
XM_011536050.2 chr6:g.117317229G>T c.6076C>A p.L2026M RefSeq GRCh38/hg38

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  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
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  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ROS1 fusion ROS1 L1951R ROS1 L2026M lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion progressed after 17 months of treatment with Xalkori (crizotinib), and was found to have acquired two additional mutations in trans, ROS1 L2026M and ROS1 L1951R, and cells derived from this patient showed partially decreased SHP2 and ERK1/2 signaling and ROS1 activation (PMID: 29636358). 29636358
ROS1 fusion ROS1 L1951R ROS1 L2026M lung non-small cell carcinoma resistant Ceritinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient co-harboring a ROS1 fusion, and two other mutations in trans, ROS1 L2026M, and ROS1 L1951R demonstrated resistance to treatment with Zykadia (ceritinib), and cells derived from this patient showed partially decreased SHP2 and ERK1/2 signaling and ROS1 activation (PMID: 29636358). 29636358
ROS1 rearrange ROS1 L2026M TP53 P278H lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a Phase II clinical trial, a patient with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated progression while being treated with Xalkori (crizotinib), and was found to have acquired two mutations, ROS1 L2026M and TP53 P278H (PMID: 30978502; NCT02183870). 30978502