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Gene | ROS1 |
Variant | G2032R |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | ROS1 G2032R lies within the protein kinase domain of the Ros1 protein (UniProt.org). G2032R has been associated with resistance to Ros1 tyrosine kinase inhibitors in the context of ROS1 fusions in patients (PMID: 36135089, PMID: 25033171, PMID: 29477381), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). |
Associated Drug Resistance | Y |
Category Variants Paths |
ROS1 mutant ROS1 G2032R |
Transcript | NM_002944.3 |
gDNA | chr6:g.117317184C>T |
cDNA | c.6094G>A |
Protein | p.G2032R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011536051.3 | chr6:g.117317187C>T | c.6094G>A | p.G2032R | RefSeq | GRCh38/hg38 |
NM_002944.2 | chr6:g.117317184C>T | c.6094G>A | p.G2032R | RefSeq | GRCh38/hg38 |
NM_002944 | chr6:g.117317184C>T | c.6094G>A | p.G2032R | RefSeq | GRCh38/hg38 |
XM_011536051.2 | chr6:g.117317187C>T | c.6094G>A | p.G2032R | RefSeq | GRCh38/hg38 |
NM_002944.3 | chr6:g.117317184C>T | c.6094G>A | p.G2032R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ROS1 fusion ROS1 G2032R | lung non-small cell carcinoma | predicted - sensitive | Repotrectinib | Phase I | Actionable | In a Phase I/II trial (TRIDENT-1), Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate of 59% (10/17) in patients with TKI-pretreated, ROS1 fusion-positive non-small cell lung cancer harboring ROS1 G2032R (PMID: 38197815; NCT03093116). | 38197815 |
ROS1 fusion ROS1 G2032R | Advanced Solid Tumor | predicted - sensitive | Repotrectinib | Phase I | Actionable | In a Phase I (TRIDENT-1) trial, Augtyro (repotrectinib) treatment resulted in partial response in a patient with advanced solid tumor harboring ROS1 G2032R in the context of ROS1 fusion (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116). | detail... |
ROS1 fusion ROS1 G2032R | lung non-small cell carcinoma | predicted - sensitive | Taletrectinib | Case Reports/Case Series | Actionable | In a Phase II trial (TRUST-I), Taletrectinib (DS6051b) treatment resulted in an objective response rate of 66.7% (8/12, all partial responses) in patients with non-small cell lung cancer harboring ROS1 fusions with secondary ROS1 G2032R mutations (PMID: 38822758; NCT04395677). | 38822758 |
ROS1 fusion ROS1 G2032R | lung non-small cell carcinoma | predicted - sensitive | NUV-520 | Phase I | Actionable | In a Phase I trial (ARROS-1), NUV-520 treatment resulted in 6 partial responses among 12 patients with non-small cell lung cancer harboring a ROS1 fusion including a partial response in 5 of 7 patients harboring a ROS1 fusion with ROS1 G2032R (Eu J Cancer 2022 Vol 174, Supp 1:S6-S7; NCT05118789). | detail... |