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Molecular Profile	Treatment Approach
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Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
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Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
KIT	T670V	missense	unknown	KIT T670V lies within the protein kinase domain of the Kit protein (UniProt.org). T670V has been identified in the scientific literature (PMID: 31270078), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024).
KIT	Y672C	missense	unknown	KIT Y672C lies within the protein kinase domain of the Kit protein (UniProt.org). Y672C is associated with decreased KIT inhibitor sensitivity when in the context of an activating KIT mutation in culture (PMID: 31270078), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024).
KIT	D677N	missense	unknown	KIT D677N lies within the protein kinase domain of the Kit protein (UniProt.org). D677N is associated with drug resistance when in the context of an activating KIT mutation (PMID: 31270078), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024).	Y

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
KIT T670I	gastrointestinal stromal tumor	predicted - resistant	Avapritinib	Phase I	Actionable	In a Phase I trial, patients with gastrointestinal stromal tumors harboring either KIT V654A or KIT T670I demonstrated decreased overall response rate (0%, 0/25 vs. 26%, 22/84) and increased progressive disease rate (72% vs 23%) compared to those without either KIT mutation when treated with Ayvakit (avapritinib) (PMID: 31270078; NCT02508532).	31270078
KIT V654A	gastrointestinal stromal tumor	predicted - resistant	Avapritinib	Phase I	Actionable	In a Phase I trial, patients with gastrointestinal stromal tumors harboring either KIT V654A or KIT T670I demonstrated decreased overall response rate (0%, 0/25 vs. 26%, 22/84) and increased progressive disease rate (72% vs 23%) compared to those without either KIT mutation when treated with Ayvakit (avapritinib) (PMID: 31270078; NCT02508532).	31270078
KIT D677N KIT D816V	Advanced Solid Tumor	predicted - sensitive	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT D677N demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078).	31270078
KIT D677N KIT D816V	Advanced Solid Tumor	resistant	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT D677N demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078).	31270078
KIT D816V	Advanced Solid Tumor	sensitive	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Ayvakit (avapritinib) in culture, demonstrating decreased cell proliferation (PMID: 31270078).	31270078
KIT D816V	Advanced Solid Tumor	sensitive	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078).	31270078
KIT N655K KIT D816V	Advanced Solid Tumor	predicted - sensitive	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT N655K demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078).	31270078
KIT N655K KIT D816V	Advanced Solid Tumor	resistant	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT N655K demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078).	31270078
KIT T670A KIT D816V	Advanced Solid Tumor	sensitive	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670A demonstrated sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078).	31270078
KIT T670A KIT D816V	Advanced Solid Tumor	sensitive	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670A were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078).	31270078
KIT T670I KIT D816V	Advanced Solid Tumor	decreased response	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670I demonstrated a decreased response compared to cells expressing KIT D816V alone when treated with Rydapt (midostaurin) in culture (PMID: 31270078).	31270078
KIT T670I KIT D816V	Advanced Solid Tumor	resistant	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670I demonstrated resistance to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078).	31270078
KIT T670V KIT D816V	Advanced Solid Tumor	sensitive	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670V were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078).	31270078
KIT T670V KIT D816V	Advanced Solid Tumor	predicted - resistant	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670V demonstrated some resistance to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078).	31270078
KIT V560D	gastrointestinal stromal tumor	predicted - sensitive	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing KIT V560D were sensitive to treatment with Ayvakit (avapritinib) in culture, demonstrating decreased cell growth (PMID: 31270078).	31270078
KIT V560D KIT V654A	Advanced Solid Tumor	decreased response	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 31270078).	31270078
KIT V654A KIT D816V	Advanced Solid Tumor	predicted - sensitive	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078).	31270078
KIT V654A KIT D816V	Advanced Solid Tumor	resistant	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078).	31270078
KIT Y672C KIT D816V	Advanced Solid Tumor	predicted - sensitive	Avapritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT Y672C demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078).	31270078
KIT Y672C KIT D816V	Advanced Solid Tumor	decreased response	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing KIT D816V and KIT Y672C demonstrated a decreased response compared to cells expressing KIT D816V alone when treated with Rydapt (midostaurin) in culture (PMID: 31270078).	31270078

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