ALK L1198F

CI-VAR-00002212Explore in graph →NP_004295.2:p.Leu1198PheNM_004304.4:c.3592C>TCIViC 1275 rs751306825

Curated evidence

Evidence by cancer (8 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–8 of 8 evidence items across 2 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Non-Small Cell Carcinoma4
ALK L1198F	(predisposing)	Predisposing	C	Supports Predisposition	3	rejected	EID2942 In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted t… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
ALK L1198F	Crizotinib	Predictive	C	Supports Sensitivity Response	—	submitted	EID4782 In a metastatic EML4-ALK rearranged non-small cell lung carcinoma patient harboring ALK C1156Y (a known crizotinib resistance mutation) and ALK L1198F co-mutations, ALK L1198F was associated with rese… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic

ClinVar

Clinical significance (0)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

Data not yet available

No ClinVar interpretation attached to this variant.

Malignant Neoplasm4
EML4::ALK Fusion AND ALK G1202R AND ALK L1198F	Alectinib + Brigatinib + Ceritinib + LorlatinibSubstitutes	Predictive	D	Supports Resistance	4	submitted	EID7595 EML4-ALK expressing Ba/F3 cell lines with the compound ALK mutation G1202R/L1198F were found to be resistant to lorlatinib as well as second-line ALK inhibitors. Ba/F3 cells expressing variant 1 (E13;… (full text at CIViC) PMID 29650534 · Yoda et al., 2018 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1198F	Crizotinib	Predictive	D	Supports Sensitivity Response	4	submitted	EID7603 The EML4-ALK fusion resistance mutation L1198F was shown to increase sensitivity of cells to crizotinib in vitro. In cell survival assays Ba/F3 cells expressing L1198F mutated EML4-ALK had even greate… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y	Crizotinib	Predictive	D	Supports Sensitivity Response	4	submitted	EID7605 The EML4-ALK fusion compound resistance mutation C1156Y-L1198F was shown to re-sensitize cells to crizotinib in vitro. In cell survival assays Ba/F3 cells expressing C1156Y-L1198F mutated EML4-ALK wer… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1198F AND ALK L1196M	Crizotinib	Predictive	D	Does Not Support Resistance	3	submitted	EID7594 Ba/F3 cell lines expressing the EML4-ALK fusion with compound mutation L1196M/L1198F were sensitive to crizotinib. Cell lines expressing variant 1 (E13; A20) of EML4-ALK had an IC50 of 45.6 +/- 7.1, w… (full text at CIViC) PMID 29650534 · Yoda et al., 2018 · Open in CIViC	civic