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Gene ROS1
Variant S1986F
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions ROS1 S1986F lies within the protein kinase domain of the Ros1 protein (UniProt.org). S1986F results in increased colony formation that is not statistically significant relative to wild-type Ros1 and increased Ros1 phosphorylation in culture (PMID: 37587872), and has been demonstrated to occur as a secondary drug resistance mutation and increase cell migration and invasion in the context of ROS1 fusions in culture (PMID: 36265718, PMID: 27401242, PMID: 32776005), and therefore, is predicted to lead to a gain of Ros1 protein function.
Associated Drug Resistance Y
Category Variants Paths

ROS1 mutant ROS1 act mut ROS1 S1986F

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Transcript NM_002944.3
gDNA chr6:g.117318236G>A
cDNA c.5957C>T
Protein p.S1986F
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002944 chr6:g.117318236G>A c.5957C>T p.S1986F RefSeq GRCh38/hg38
NM_002944.2 chr6:g.117318236G>A c.5957C>T p.S1986F RefSeq GRCh38/hg38
NM_002944.3 chr6:g.117318236G>A c.5957C>T p.S1986F RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ROS1 S1986F Advanced Solid Tumor predicted - sensitive SAF-189s Preclinical - Biochemical Actionable In a preclinical study, SAF-189s inhibited kinase activity of a transformed cell line expressing ROS1 S1986F in culture (PMID: 32918045). 32918045
ROS1 S1986F Advanced Solid Tumor predicted - sensitive Lorlatinib Preclinical - Biochemical Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 S1986F in culture (PMID: 32918045). 32918045