Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
| Gene | KIT |
| Variant | S501_A502dup |
| Impact List | duplication |
| Protein Effect | gain of function - predicted |
| Gene Variant Descriptions | KIT S501_A502dup (also referred to as A502_Y503insSA) indicates the insertion of two duplicate amino acids, serine (S)-501 through alanine (A)-502, in Ig-like C2-type domain 5 of the Kit protein (UniProt.org). S501_A502dup results in constitutive phosphorylation of Kit in primary and cultured cells (PMID: 22324351), and therefore, is predicted to lead to a gain of Kit protein function. |
| Associated Drug Resistance | |
| Category Variants Paths |
KIT mutant KIT act mut KIT S501_A502dup KIT mutant KIT exon9 KIT exon 9 ins KIT S501_A502dup |
| Transcript | NM_000222.3 |
| gDNA | chr4:g.54726011_54726016 |
| cDNA | c.1501_1506 |
| Protein | p.S501_A502 |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_000222 | chr4:g.54726016_54726017insAGCGCA | c.1506_1507insAGCGCA | p.S501_A502dup | RefSeq | GRCh38/hg38 |
| NM_001385286.1 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502 | RefSeq | GRCh38/hg38 |
| NM_001093772.1 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502dup | RefSeq | GRCh38/hg38 |
| XM_017008178 | chr4:g.54726016_54726017insAGCGCA | c.1506_1507insAGCGCA | p.S501_A502dup | RefSeq | GRCh38/hg38 |
| NM_000222.2 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502dup | RefSeq | GRCh38/hg38 |
| NM_000222.3 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502 | RefSeq | GRCh38/hg38 |
| XM_017008178.1 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502dup | RefSeq | GRCh38/hg38 |
| NM_001385285.1 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502 | RefSeq | GRCh38/hg38 |
| NM_001093772.1 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502 | RefSeq | GRCh38/hg38 |
| NM_001093772.2 | chr4:g.54726011_54726016 | c.1501_1506 | p.S501_A502 | RefSeq | GRCh38/hg38 |
| NM_001093772 | chr4:g.54726016_54726017insAGCGCA | c.1506_1507insAGCGCA | p.S501_A502dup | RefSeq | GRCh38/hg38 |
| XM_017008180 | chr4:g.54726016_54726017insAGCGCA | c.1506_1507insAGCGCA | p.S501_A502dup | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| KIT act mut | skin melanoma | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org). | detail... |
| KIT act mut | gastrointestinal stromal tumor | sensitive | Pexidartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX3397 inhibited growth of gastrointestinal stromal tumor cell lines harboring KIT activating mutations in culture and in cell line xenograft models (PMID: 24583793). | 24583793 |
| KIT act mut | skin melanoma | sensitive | Ripretinib | Guideline | Actionable | Qinlock (ripretinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org). | detail... |
| KIT act mut | melanoma | predicted - sensitive | Regorafenib | Case Reports/Case Series | Actionable | In a clinical case study, Stivarga (regorafenib) treatment demonstrated safety and preliminary activity in patients with melanoma harboring activating mutations in KIT, resulting in an overall response rate of 100% (7/7, 1 complete and 6 partial responses), with median duration of response and median progression-free survival not reached and response ongoing in 4 patients at a median follow-up of 43 weeks (Ann Oncol (2024) 35 (suppl_2): S743-S744). | detail... |
| KIT act mut | skin melanoma | sensitive | Nilotinib | Guideline | Actionable | Tasigna (nilotinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org). | detail... |
| KIT act mut | skin melanoma | sensitive | Dasatinib | Guideline | Actionable | Sprycel (dasatinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org). | detail... |
| KIT act mut | gastrointestinal stromal tumor | not applicable | N/A | Guideline | Diagnostic | KIT activating mutations aid the diagnosis of gastrointestinal stromal tumor (NCCN.org). | detail... |
| KIT act mut | Advanced Solid Tumor | sensitive | PLX9486 | Preclinical | Actionable | In a preclinical study, PLX9486 inhibited KIT mutations, including exon 17 mutations, and demonstrated in vivo and in vitro activity against tumors harboring KIT exon 17 mutations (Cancer Res February 1, 2016 76; IA32). | detail... |
| KIT act mut | gastrointestinal stromal tumor | sensitive | Cabozantinib | Preclinical | Actionable | In a preclinical study, Cometriq (cabozantinib) decreased cell viability in imatinib-sensitive and resistant gastrointestinal stromal tumor (GIST) cell lines harboring KIT activating mutations in culture, and induced tumor regression in KIT-mutant GIST mouse models (PMID: 25836719). | 25836719 |
| KIT mutant | melanoma | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) treatment demonstrated manageable safety and preliminary efficacy in patients with KIT-mutated melanoma, and led to an objective response rate of 23% (6/26, 1 complete and 5 partial responses), a median progression-free survival of 7.3 months, and a median duration of response of 9.1 months (PMID: 35753087; NCT02571036). | 35753087 |
| KIT mutant | gastrointestinal stromal tumor | sensitive | Imatinib + Infigratinib | Preclinical - Pdx | Actionable | In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antitumor activity in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT mutations (PMID: 25673643). | 25673643 |
| KIT mutant | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 4% (1/25), durable partial response in 16% (4/25), and stable disease in 56% (14/25) of melanoma patients harboring KIT mutations (PMID: 28843487; NCT01168050). | 28843487 |
| KIT mutant | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment in patients with melanoma harboring KIT mutations resulted in an overall response rate of 26.2% (11/42), which included 11 patients with a partial response, a median duration of response of 7.1 months, and an overall survival of 18 months (PMID: 28327988; NCT01028222). | 28327988 |
| KIT mutant | gastrointestinal stromal tumor | not applicable | N/A | Clinical Study | Diagnostic | KIT mutations are used in the diagnosis of gastrointestinal stromal tumors (PMID: 25193432, PMID: 26276366, PMID: 25729899). | 25193432 26276366 25729899 |
| KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Avapritinib | Phase I | Actionable | In a Phase I (NAVIGATOR) trial, Ayvakit (avapritinib) treatment resulted in an objective response rate of 13% (7/52, 7 partial responses) and a disease control rate of 63% (33/52) in patients with KIT-mutant gastrointestinal stromal tumor (The CTOS 2018 Annual Meeting, Nov 14-17, Rome Italy, Paper 012 3027631; NCT02508532). | detail... |
| KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) demonstrated preliminary safety and efficacy in patients with advanced solid tumors, including KIT-mutant gastrointestinal stromal tumor (GIST), with 1 patient harboring KIT exon 11 and 17 mutations demonstrating a partial response, and 7/7 KIT-mutant GIST patients demonstrating a partial metabolic response (EORTC-NCI-AACR 2016, Abs 7LBA). | detail... |
| KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) was well tolerated, resulted in an objective response in 11.3% (16/142, 16 partial responses) and stable disease in 61.3% (87/142) of patients with advanced gastrointestinal stromal tumor harboring KIT (exon 11, n=103; exon 9, n=26; other, n=6) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months (PMID: 32804590; NCT02571036). | 32804590 |
| KIT exon9 | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). | 25239608 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Regorafenib | Guideline | Actionable | Stivarga (regorafenib) is included in guidelines as third-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... |
| KIT exon9 | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
| KIT exon9 | melanoma | predicted - sensitive | Regorafenib | Case Reports/Case Series | Actionable | In a Phase II trial, second or later-line Stivarga (regorafenib) treatment resulted in a disease control rate of 73.9% (17/23, 2 complete responses, 5 partial responses), an objective response rate of 30.4% (7/23), and median overall survival (mOS) of 21.5 months in patients with melanoma harboring KIT exon 9, 11, 13, or 17 mutations, and improved mOS in patients with non-exon 11 mutations compared to patients with exon 11 mutations (24.9 mo vs 18.3 mo, P=0.042) (PMID: 37741071; NCT02501551). | 37741071 |
| KIT exon9 | gastrointestinal stromal tumor | no benefit | Ponatinib | Phase II | Actionable | In a Phase II trial, Iclusig (ponatinib) treatment did not result in clinical benefit in gastrointestinal stromal tumor patients with KIT exon 9 mutations who had failed prior tyrosine kinase inhibitor treatment (PMID: 35091442; NCT01874665). | 35091442 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Sunitinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, GIST patients with KIT exon 9 mutations showed improved progression-free survival (PFS), overall survival, and objective response rate (ORR) compared to patients with exon 11 mutations, with a median PFS of 12.3 months vs. 7.0 months, and an ORR of 19% (8/42) vs. 6% (9/143) following treatment with Sutent (sunitinib) (PMID: 26772734). | 26772734 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Sunitinib | Guideline | Actionable | Sutent (sunitinib) is included in guidelines as second-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | detail... 34560242 |
| KIT exon9 | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, Stivarga (regorafineb) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). | 25239608 |
| KIT exon9 | gastrointestinal stromal tumor | no benefit | Imatinib + Infigratinib | Phase I | Actionable | In a Phase I trial, Truseltiq (infigratinib) and Gleevec (imatinib) combination therapy resulted in stable disease as best response in 58% (7/12) of patients with advanced gastrointestinal stromal tumor harboring KIT mutations in exon 9 (n=3), exon 11 (n=10), or other (n=3), however, the trial was discontinued due to toxicity concerns (PMID: 30101387). | 30101387 |
| KIT exon9 | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Ripretinib | Guideline | Actionable | Qinlock (ripretinib) is included in guidelines as fourth-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) was well tolerated, resulted in an objective response in 11.3% (16/142, 16 partial responses) and stable disease in 61.3% (87/142) of patients with advanced gastrointestinal stromal tumor harboring KIT (n=135) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months, 18.3% (26/142) of the patients harbored KIT exon 9 mutations (PMID: 32804590; NCT02571036). | 32804590 |
| KIT exon9 | gastrointestinal stromal tumor | no benefit | Imatinib + Spartalizumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Spartalizumab (PDR001) and Gleevec (imatinib) was tolerable but demonstrated limited efficacy in Phase II, with an objective response rate of 0% (0/29), a disease control rate of 37.9% (11/29), median progression-free survival of 2.3 months, and overall survival of 9.5 months in patients with gastrointestinal stromal tumor harboring KIT exon 9 (n=8), exon 11 (n=17), or other mutations (PMID: 38662455). | 38662455 |
| KIT exon9 | gastrointestinal stromal tumor | predicted - sensitive | IDRX-42 | Phase I | Actionable | In a Phase I trial, IDRX-42 treatment demonstrated safety and resulted in 9 partial responses among 39 evaluable patients with gastrointestinal stromal tumors harboring a KIT exon 11 (n=27), exon 9 (n=13), or exon 8 (n=2) mutation with a clinical benefit rate of 71% overall and 100% as second-line treatment (J Clin Oncol 42, 2024 (suppl 16; abstr 11501); NCT05489237). | detail... |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations, as adjuvant therapy for patients with localized disease and as first-line therapy for patients with locally advanced, unresectable, or metastatic disease (PMID: 34560242; ESMO.org). | 34560242 detail... |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for patients with gastrointestinal stromal tumor (GIST) harboring KIT exon 9 mutations (NCCN.org). | detail... |