ALK F1245C

CI-VAR-00001075Explore in graph →NP_004295.2:p.Phe1245CysNM_004304.4:c.3734T>GClinVar 217856 CIViC 549 rs863225283

Curated evidence

Evidence by cancer (6 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 1–6 of 6 evidence items across 3 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 Carcinoma2
EML4::ALK Fusion AND ALK F1245C	Ceritinib	Predictive	C	Supports Sensitivity Response	3	accepted	EID1338 A 52 year old male never smoker was diagnosed with stage IV NSCLC adenocarcinoma and was treated with chemotherapy with eventual disease progression. He tested positive for ALK rearrangement via break… (full text at CIViC) PMID 26775591 · Kodityal et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1245C	Crizotinib	Predictive	C	Supports Resistance	2	accepted	EID1339 A 52 year old with a non-smoking history was diagnosed with stage IV NSCLC-adenocarcinoma and treated with chemotherapy. Upon disease progression, the initial diagnostic biopsy tested positive for AL… (full text at CIViC) PMID 26775591 · Kodityal et al., 2016 · Open in CIViC

ClinVar

Clinical significance (1)

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

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
217856	Pathogenic	no assertion criteria provided	0	Neuroblastoma, susceptibility to, 3; Neuroblastoma	somatic	2	Oct 07, 2015	clinvar

Malignant Neoplasm2
EML4::ALK Fusion AND ALK F1245C	Crizotinib	Predictive	D	Supports Resistance	2	accepted	EID1337 A Ba/F3 cell line expressing EML4-ALK variant 1 was created, and then exposed to the DNA modifying agent ENU. Cells were subsequently cultured in 96 well plates at increasing concentrations of crizoti… (full text at CIViC) PMID 22034911 · Zhang et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1245C	Crizotinib	Predictive	D	Supports Resistance	3	submitted	EID11067 Ba/F3 cells with EML4::ALK were subjected to mutagen N-ethyl-N-nitrosourea and then incubated without IL3 in 250, 500, 720, 1000, 1440, or 2000 nm crizotinib. The ten most frequently seen mutants we… (full text at CIViC) PMID 22034911 · Zhang et al., 2011 · Open in CIViC	civic

Neuroblastoma2
ALK F1245C	Crizotinib	Predictive	C	Supports Resistance	3	accepted	EID1333 A participant in Children's Oncology Group (COG) study AVDL0912 with measurable neuroblastoma mutated at ALK F1245C was administered crizotinib at 100mg twice daily. The patient showed progressive di… (full text at CIViC) PMID 23598171 · Mossé et al., 2013 · Open in CIViC	civic
ALK F1245C	Lorlatinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID1330 Patient derived xenografts of neuroblastoma Felix cells with F1245C ALK mutation in CB17 SCID mice showed growth inhibition with crizotinib treatment over control, and mice had improved duration of ev… (full text at CIViC) PMID 26554404 · Infarinato et al., 2016 · Open in CIViC	civic