Gene Detail

Gene Symbol KIT
Synonyms C-Kit | CD117 | MASTC | PBT | SCFR
Gene Description KIT, mast/stem cell growth factor receptor Kit, is a receptor tyrosine kinase that binds the stem cell factor (SCF) ligand to activate PI3K, JAK/STAT, and MAPK pathways to promote cell survival and proliferation (PMID: 23181448, PMID: 29704617). Activating Kit mutations are driver mutations in a variety of cancers, particularly in gastrointestinal stromal tumors (PMID: 23127174, PMID: 29704617), acute myeloid leukemia (AML), melanomas, and seminomas (PMID: 29704617).
Entrez Id 3815
Chromosome 4
Map Location 4q12
Canonical Transcript NM_000222

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
V559C missense unknown KIT V559C lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). V559C has been identified in sequencing studies (PMID: 25695690), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V559_V560delinsS indel gain of function - predicted KIT V559_V560delinsS results in a deletion of 2 amino acids within the juxtamembrane domain of the Kit protein, combined with the insertion of a serine (S) at the same site (PMID: 12879016). V559_V560delinsS has not been characterized, but is predicted to lead to a gain of Kit protein function based on the effect of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
W557C missense unknown KIT W557C lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). W557C has been identified in the scientific literature (PMID: 28327988) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
L576F missense unknown KIT L576F lies within the juxtamembrane domain of the Kit protein (PMID: 17372901). L576F has been identified in sequencing studies (PMID: 21325067), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V559_V560del deletion gain of function KIT V559_V560del results in the deletion of two amino acids in the juxtamembrane domain of the Kit protein from amino acids 559 to 560 (UniProt.org). V559_V560del confers a gain of function on Kit, as indicated by constitutive phosphorylation of Kit, is transforming in cell culture, and promotes tumor formation in mice (PMID: 9797363).
V825I missense unknown KIT V825I lies within the protein kinase domain of the Kit protein (UniProt.org). V825I has been identified in sequencing studies (PMID: 16460801), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K642E missense gain of function KIT K642E lies within the tyrosine kinase domain 1 of the Kit protein (PMID: 15990278). K642E results in constitutive phosphorylation of Kit and activation of downstream signaling (PMID: 15990278, PMID: 19802003), as well as transformation of cultured cells (PMID: 11073817).
Q556_K558del deletion gain of function - predicted KIT Q556_K558del results in the deletion of three amino acids in the juxtamembrane domain of the Kit protein from amino acids 556 to 558 (PMID: 12879016). Q556_K558del results in constitutive phoaphorylation of Kit in culture in one study (PMID: 30094412) and therefore, is predicted to lead to a gain of Kit protein function.
L576P missense gain of function KIT L576P lies within the juxtamembrane domain of the Kit protein (PMID: 17372901). L576P confers a gain of function to Kit, as indicated by constitutive phosphorylation of Kit, and is transforming in cell culture (PMID: 17372901).
G812V missense unknown KIT G812V lies within the protein kinase domain of the Kit protein (UniProt.org). G812V has been identified in the scientific literature (PMID: 25960657) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown.
mutant unknown unknown KIT mutant indicates an unspecified mutation in the KIT gene.
P551_V555delinsTL indel gain of function - predicted KIT P551_V555delinsTL results in a deletion of 5 amino acids within the juxtamembrane domain of the Kit protein, combined with the insertion of a threonine (T) and a leucine (L) at the same site (PMID: 12879016). P551_V555delinsTL has not been characterized, but is predicted to lead to a gain of function based on the effect of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
E490* nonsense loss of function - predicted KIT E490* results in a premature truncation of the Kit protein at amino acid 490 of 976 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), E490* is predicted to lead to a loss of Kit protein function.
wild-type none no effect Wild-type KIT indicates that no mutation has been detected within the KIT gene.
K550_W557del deletion gain of function - predicted KIT K550_W557del results in the deletion of eight amino acids in the juxtamembrane domain of the Kit protein from amino acids 550 to 557 (PMID: 16226710). K550_W557del has not been characterized, however similar Kit exon 11 deletions are activating, thus K550_W557del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
M552_D572del deletion gain of function - predicted KIT M552_D572del results in the deletion of twenty one amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 to 572 (PMID: 16226710). M552_D572del has not been characterized, however similar Kit exon 11 deletions are activating, thus M552_D572del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
Y553C missense unknown KIT Y553C lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). Y553C has been identified in sequencing studies (PMID: 23106360), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
D820N missense unknown KIT D820N lies within the protein kinase domain of the Kit protein (UniProt.org). D820N has been identified as a secondary mutation associated with imatinib-resistance (PMID: 18628470), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Jul 2018). Y
Y553_W557del deletion gain of function - predicted KIT Y553_W557del results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 553 to 557 (PMID: 16226710). Y553_W557del has not been characterized, however similar Kit exon 11 deletions are activating, thus Y553_W557del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 12727838).
N80S missense unknown KIT N80S lies within the Ig-like C2-type domain 1 of the Kit protein (UniProt.org). N80S has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
Y570H missense unknown KIT Y570H lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). Y570H has been identified in sequencing studies (PMID: 21642685) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V556_L576del deletion gain of function - predicted KIT V556_L576del results in the deletion of twenty-one amino acids in the juxtamembrane domain of the Kit protein (PMID: 12879016). V556_L576 has not been characterized, however similar Kit exon 11 deletions are activating, thus V556_L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
D820E missense unknown KIT D820E lies within the protein kinase domain of the Kit protein (UniProt.org). D820E has been associated with secondary drug resistance (PMID: 19861442), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Jul 2018). Y
R634L missense unknown KIT R634L lies within the protein kinase domain of the Kit protein (UniProt.org). R634L has been identified in the scientific literature (PMID: 28843487), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Aug 2018).
S501_A502dup insertion gain of function - predicted KIT S501_A502dup (also referred to as A502_Y503insSA) indicates the insertion of 2 duplicate amino acids, serine (S)-501 through alanine (A)-502, in the 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 in one study (PMID: 22324351) and therefore, is predicted to lead to a gain of Kit protein function.
Y570_L576del deletion gain of function - predicted KIT Y570_L576del results in the deletion of seven amino acids in the juxtamembrane domain of the Kit protein from amino acids 570 to 576 (PMID: 16226710). Y570_L576del has not been characterized, however similar Kit exon 11 deletions are activating, thus Y570_L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
N822Y missense gain of function - predicted KIT N822Y lies within the protein kinase domain of the Kit protein (UniProt.org). N822Y results in constitutive phosphorylation of Kit in culture in one study (PMID: 30094412) and therefore, is predicted to lead to a gain of Kit protein function.
M552_Y553del deletion gain of function - predicted KIT M552_Y553del results in the deletion of two amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 to 553 (PMID: 15897563). M552_Y553del has not been characterized, however similar Kit exon 11 deletions are activating, thus M552_Y553del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
D820A missense unknown KIT D820A lies within the protein kinase domain of the Kit protein (UniProt.org). D820A has been demonstrated to occur as a secondary drug resistance mutation in Kit (PMID: 16954519), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Jul 2018). Y
M552_E554del deletion gain of function - predicted KIT M552_E554del results in the deletion of three amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 to 554 (PMID: 12879016). M552_E554del has not been characterized, however similar Kit exon 11 deletions are activating, thus M552_E554del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
Q556_W557del deletion gain of function - predicted KIT Q556_W557del results in the deletion of two amino acids in the juxtamembrane domain of the Kit protein from amino acids 556 to 557 (PMID: 16226710). Q556_W557del has not been characterized, however similar Kit exon 11 deletions are activating, thus Q556_W557del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
P551_M552delinsL indel gain of function - predicted KIT P551_M552delinsL results in the deletion of 2 amino acids in the juxtamembrane domain of the Kit protein from amino acids 551 to 552, combined with the insertion of a leucine (L) at the same site (PMID: 16226710). P551_M552delinsL has not been characterized, but is predicted to activate Kit based on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
V555_E562del deletion gain of function - predicted KIT V555_E562del results in the deletion of eight amino acids in the juxtamembrane domain of the Kit protein from amino acids 555 to 562 (PMID: 12879016). V555_E562del has not been characterized, however similar Kit exon 11 deletions are activating, thus V555_E562del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
E554K missense unknown KIT E554K lies within the cytoplasmic domain of the Kit protein (UniProt.org). E554K has been identified in sequencing studies (PMID: 21642685), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V560E missense gain of function - predicted KIT V560E lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). V560E has been identified in the scientific literature (PMID: 25695690) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
exon9 unknown unknown KIT exon 9 indicates an unspecified mutation has occurred in exon 9 of the KIT gene.
W557_K558delinsE indel gain of function - predicted KIT W557_K558delinsE results in the deletion of 2 amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 558, combined with the insertion of a glutamic acid (E) at the same site (PMID: 16226710). W557_K558delinsE has not been characterized, but is predicted to activate Kit basing on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
E695* nonsense loss of function - predicted KIT E695* results in a premature truncation of the Kit protein at amino acid 695 of 976 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), E695* is predicted to lead to a loss of Kit protein function.
T417_Y418delinsH deletion gain of function - predicted KIT T417_Y418delinsH results in the deletion of two amino acids in the Ig-like C2-type 5 domain of the Kit protein from amino acids 417 to 418, combined with the insertion of an Histidine (H) at the same site (UniProt.org). T417_Y418delinsH has not been characterized, however similar Kit exon 8 mutations are activating, thus T417_Y418delinsH is predicted to lead to a gain of Kit protein function (PMID: 16015387, PMID: 15618474, PMID: 20484085).
T632I missense unknown KIT T632I lies within the protein kinase domain of the Kit protein (UniProt.org). T632I has been identified in sequencing studies (PMID: 21325067), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2017).
W557_V559delinsF indel unknown KIT W557_V559delinsF results in the deletion of 3 amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 559, combined with the insertion of a phenylalanine (F) at the same site (PMID: 16226710). KIT W557_V559delinsF has been identified in the scientific literature (PMID: 25926077), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V559G missense gain of function - predicted KIT V559G lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). V559G results in constitutive phosphorylation of Kit in patient sample in one stufy (PMID: 15897563) and therefore, is predicted to lead to a gain of Kit protein function.
W557Lfs*5 frameshift loss of function - predicted KIT W557Lfs*5 indicates a shift in the reading frame starting at amino acid 557 and terminating 5 residues downstream causing a premature truncation of the 976 amino acid Kit protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W557Lfs*5 is predicted to result in a loss of Kit protein function.
D820G missense unknown KIT D820G lies within the protein kinase domain of the Kit protein (UniProt.org). D820G has been identified as a secondary mutation associated with imatinib resistance (PMID: 18488160), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Jul 2018). Y
K558* nonsense loss of function - predicted KIT K558* results in a premature truncation of the Kit protein at amino acid 558 of 976 (UniProt.org). Due to the loss of protein kinase domain (UniProt.org), K558* is predicted to lead to a loss of Kit protein function.
D52N missense unknown KIT D52N lies within the extracellular domain of the Kit protein (UniProt.org). D52N has been identified in the scientific literature (PMID: 15167915), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Aug 2018).
K550_K558del deletion gain of function KIT K550_K558del results in the deletion of nine amino acids in the juxtamembrane domain of the Kit protein from amino acids 550 to 558 (PMID: 15824741). K550_K558del results in constitutive phosphorylation of Kit, transformation of cultured cells, and tumor formation in animal models (PMID: 9438854).
Y578_D579del deletion gain of function - predicted KIT Y578_D579del results in the deletion of two amino acids in the juxtamembrane domain of the Kit protein from amino acids 578 to 579 (UniProt.org). Y578_D579del has not been characterized, however similar Kit exon 11 deletions are activating, thus Y578_D579del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
W557del missense gain of function - predicted KIT W557del results in the deletion of an amino acid in the juxtamembrane domain of the Kit protein at amino acids 557 (PMID: 12918066). W557del has not been characterized, however similar Kit exon 11 deletions are activating, thus W557del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 9797363).
R634W missense gain of function KIT R634W lies within the protein kinase domain of the Kit protein (UniProt.org). R634W confers a gain of function to the Kit protein as demonstrated by constitutive Kit phosphorylation, increased Stat3 and Stat5 phosphorylation, and is transforming in cell culture (PMID: 15790786).
V555_L576del deletion gain of function - predicted KIT V555_L576del results in the deletion of twenty-two amino acids in the juxtamembrane domain of the Kit protein from amino acids 555 to 576 (PMID: 12879016). V555_I576del has not been characterized, however similar Kit exon 11 deletions are activating, thus V555_I576del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
D816E missense unknown KIT D816E lies within the protein kinase domain of the Kit protein (UniProt.org). D816E has been identified in the scientific literature (PMID: 29100343, PMID: 29093181) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558_Y570delinsR indel gain of function - predicted KIT K558_Y570delinsR results in the deletion of thirteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 570, combined with the insertion of an arginine (R) at the same site (PMID: 16226710). K558_Y570delinsR has not been characterized, but is predicted to activate Kit basing on effects of similar mutations (PMID: 9438854, PMID: 15365079).
W557F missense unknown KIT W557F lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). W557F has been identified in the scientific literature (PMID: 19585585), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
K558_V559insNP insertion unknown KIT K558_V559insNP results in an insertion of two amino acids in the juxtamembrane domain of the Kit protein between amino acids 558 and 559 (PMID: 16226710). K558_V559insNP has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V555_Q556del deletion gain of function - predicted KIT V555_Q556del results in the deletion of two amino acids in the juxtamembrane domain of the Kit protein from amino acids 555 to 556 (PMID: 12879016). V555_Q556del has not been characterized, however similar Kit exon 11 deletions are activating, thus V555_Q556del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
V559_G565del deletion gain of function - predicted KIT V559_G565del results in the deletion of seven amino acids in the juxtamembrane domain of the Kit protein from amino acids 559 to 565 (PMID: 12879016). V559_G565del has not been characterized, however similar Kit exon 11 deletions are activating, thus V559_G565del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
M552_V559delinsI indel gain of function - predicted KIT M552_V559delinsI results in the deletion of 8 amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 to 559, combined with the insertion of an isoleucine (I) at the same site (PMID: 16226710). M552_V559delinsI has not been characterized, but is predicted to activate Kit based on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
I653T missense unknown KIT I653T lies within the protein kinase domain of the Kit protein (UniProt.org). I653T has been identified in the scientific literature (PMID: 21690468), but has not been been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
P577_E583dup duplication unknown KIT P577_E583dup (also referred to as E583_F584insPYDHKWE) indicates the insertion of 7 duplicate amino acids, proline (P)-577 through glutamic acid (E)-583, in the juxtamembrane domain of the Kit protein (PMID: 16226710). P577_E583dup has not been characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
K550_V559del deletion gain of function - predicted KIT K550_V559del results in the deletion of ten amino acids in the juxtamembrane domain of the Kit protein from amino acids 550 to 559 (PMID: 16226710). K550_V559del has not been characterized, however similar Kit exon 11 deletions are activating, thus K550_V559del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
V559A missense gain of function KIT V559A lies within the juxtamembrane domain of the Kit protein (PMID: 15837988). V559A results in constitutive phosphorylation of Kit and increased Mapk and Akt activation in patient samples and cultured cells (PMID: 15837988, PMID: 19047099).
T670I missense gain of function KIT T670I lies within the ATP pocket in the protein kinase domain of the Kit protein (PMID: 15236194, PMID: 22355224). T670I confers a gain of function on Kit as indicated by constitutive Kit phosphorylation, is transforming in cultured cells, and is associated with resistance to Kit inhibitors (PMID: 17699867, PMID: 15236194). Y
Y823D missense gain of function KIT Y823D lies within the protein kinase domain of the Kit protein (UniProt.org). Y823D confers a gain of function on Kit, as indicated by constitutive phosphorylation of Kit in cultured cells (PMID: 14695343, PMID: 20633291).
M552_K558del deletion gain of function - predicted KIT M552_K558del results in the deletion of seven amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 and 558 (PMID: 12879016). M552_K558del has not been characterized, however similar Kit exon 11 deletions are activating, thus M552_K558del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
V555_V559del deletion gain of function - predicted KIT V555_V559del results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 55 to 559 (PMID: 12879016). V555_V559del has not been characterized, however similar Kit exon 11 deletions are activating, thus V555_V559del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
D816A missense unknown KIT D816A lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 15625120). D816A has been identified in the scientific literature (PMID: 22847983) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown.
L813_V824dup missense unknown KIT L813_V824dup indicates the insertion of 12 duplicate amino acids, leucine (L)-813 through valine (V)-824, in the protein kinase domain of the Kit protein (UniProt.org). L813_V824dup has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
A502_Y503dup duplication gain of function KIT A502_Y503dup (also referred to as Y503_F504insAY) indicates the insertion of 2 duplicate amino acids, alanine (A)-502 through tyrosine (Y)-503, in the Ig-like C2-type domain 5 of the Kit protein (UniProt.org). A502_Y503dup results in constitutive phosphorylation of Kit and is transforming in cell culture (PMID: 15790786, PMID: 19865100).
K509I missense gain of function KIT K509I lies within the extracellular domain of the Kit protein (UniProt.org). K509I results in constitutive phosphorylation of Kit, increased cell proliferation, and growth factor independent survival in cell culture (PMID: 19865100).
S709F missense unknown KIT S709F lies within the protein kinase domain of the Kit protein (UniProt.org). S709F has been identified in sequencing studies (PMID: 16551858), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
F811L missense unknown KIT F811L lies within the protein kinase domain of the Kit protein (UniProt.org). F811L has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
C443S missense unknown KIT C443S lies within the Ig-like C2-type domain 5 of the Kit protein (UniProt.org). C443S has been identified in the scientific literature (PMID: 25003536), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V555I missense unknown KIT V555I lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). V555I has been identified in sequencing studies (PMID: 21478825), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K550_V555delinsI indel gain of function - predicted KIT K550_V555delinsI results in the deletion of six amino acids in the juxtamembrane domain of the Kit protein from amino acids 550 to 555, combined with the insertion of an isoleucine (L) at the same site (PMID: 16226710). K550_V555delinsI has not been characterized, but is predicted to lead to activation of Kit based on the effects of similar Kit exon 11 deletions (PMID: 9438854, PMID: 15365079).
S501_A502insSAY insertion gain of function - predicted KIT S501_A502insSAY results in an insertion of three amino acids in the Ig-like C2-type 5 domain of the Kit protein between amino acids 501 and 502 (UniProt.org). S501_A502insSAY has not been characterized, however similar insertions in this domain are activating, thus S501_A502insSAY is predicted to lead to a gain of Kit protein function (PMID: 22324351, PMID: 24127596).
amp none no effect KIT amp indicates an increased number of copies of the KIT gene. However, the mechanism causing the increase is unspecified.
E561K missense unknown KIT E561K lies within the cytoplasmic domain of the Kit protein (UniProt.org). E561K has been identified in sequencing studies (PMID: 16770100), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V560_Y578del deletion gain of function - predicted KIT V560_Y578del results in the deletion of eighteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 560 to 578 (PMID: 12879016). V560_Y578del has not been characterized, however, similar Kit exon 11 deletions are activating, thus V560_Y578del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
A794E missense unknown KIT A794E lies within the protein kinase domain of the Kit protein (UniProt.org). A794E has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
T670S missense unknown KIT T670S lies within the protein kinase domain of the Kit protein (UniProt.org). T670S has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
D419del deletion gain of function KIT D419del results in the deletion of one amino acid in the Ig-like C2-type domain 5 of the Kit protein at amino acid 419 (UniProt.org). D419del results in ligand independent phosphorylation of Kit in cell culture (PMID: 16143141, PMID: 15618474).
L576_P585dup duplication unknown KIT L576_P585dup (also referred to as P585_R586insLPYDHKWEFP) indicates the insertion of 10 duplicate amino acids, leucine (L)-576 through proline (P)-585, in the juxtamembrane domain of the Kit protein (PMID: 16226710). P585_R586insLPYDHKWEFP has not been characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
W557_V559del deletion gain of function - predicted KIT W557_V559del results in the deletion of three amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 559 (PMID: 16226710). W557_V559del has not been characterized, however similar Kit exon 11 deletions are activating, thus W557_V559del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 9797363).
G387R missense unknown KIT G387R lies within the Ig-like C2-type domain 4 of the Kit protein (UniProt.org). G387R has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
L576R missense unknown KIT L576R lies within the juxtamembrane domain of the Kit protein (PMID: 17372901). L576R has been identified in the scientific literature (PMID: 28843487), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Aug 2018).
P551_W557delinsL deletion gain of function - predicted KIT P551_W557delinsL results in the deletion of 7 amino acids in the juxtamembrane domain of the Kit protein combined with the insertion of a leucine (L) in the same location (PMID: 12879016). P551_W557delinsL has not been characterized, however similar Kit exon 11 mutations are activating, thus P551_W557delinsL is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
T67S missense unknown KIT T67S lies within the Ig-like C2-type domain 1 of the Kit protein (UniProt.org). T67S has not been characterized in the scientific literature and therefore, its effect on the Kit protein function is unknown (PubMed, Jan 2018).
W582* nonsense loss of function - predicted KIT W582* results in a premature truncation of the Kit protein at amino acid 582 of 976 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W582* is predicted to lead to a loss of Kit protein function.
M552_V559del deletion gain of function - predicted KIT M552_V559del results in the deletion of eight amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 to 559 (PMID: 20633291). K550_K558del results in constitutive Kit phosphorylation in cell culture in one study (PMID: 20633291) and therefore, is predicted to lead to a gain of Kit protein function.
Y418_D419delinsS deletion gain of function - predicted KIT Y418_D419delinsS results in the deletion of two amino acids in the Ig-like C2-type 5 domain of the Kit protein from amino acids 418 to 419, combined with the insertion of a Serine (S) at the same site (UniProt.org). Y418_D419delinsS is predicted to lead to a gain of Kit protein function because other AML-associated KIT exon 8 deletion mutations are activating (PMID: 16015387).
P551_E554del deletion gain of function - predicted KIT P551_E554del results in the deletion of 4 amino acids in the juxtamembrane domain of the Kit protein from amino acids 551 to 554 (PMID: 16226710). P551_E554del has not been characterized, however similar Kit exon 11 deletions are activating, thus P551_E554del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
V559_T574del deletion gain of function - predicted KIT V559_T574del results in the deletion of sixteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 559 to 574 (PMID: 16226710). V559_T574del has not been characterized, however similar Kit exon 11 deletions are activating, thus V559_T574del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
W853* nonsense unknown KIT W853* results in a premature truncation of the Kit protein at amino acid 853 of 976 (UniProt.org). W853* has been identified in sequencing studies (PMID: 21325067), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
M541L missense unknown KIT M541L lies within the helical domain of the Kit protein (UniProt.org). M541L is a common polymorphism that has been demonstrated to increase proliferation in the presence of ligand compared to wild-type Kit in culture (PMID: 18795925), but is not associated with tumorigenesis in the population (PMID: 16307017, PMID: 21757432) and therefore, its effect on Kit protein function is unknown.
over exp none no effect KIT over exp indicates an over expression of the KIT protein. However, the mechanism causing the over expression is unspecified.
V560A missense gain of function - predicted KIT V560A lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). V560A results in increased autophosphorylation of Kit in cultured cells in one study (PMID: 10224103) and therefore, is predicted to lead to a gain of Kit protein function.
D816H missense gain of function KIT D816H lies within the tyrosine kinase domain region 2 of the Kit protein (PMID: 19164557). D816H results in increased kinase activity, constitutive Kit phosphorylation, activation of Stat3 signaling, and transformation of cultured cells (PMID: 10362788, PMID: 11494148).
K558_E562del deletion gain of function - predicted KIT K558_E562del results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 562 (PMID: 12879016). K558_E562del has not been characterized, however similar Kit exon 11 deletions are activating, thus K558_E562del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
L631F missense unknown KIT L631F lies within the protein kinase domain of the Kit protein (UniProt.org). L631F has been identified in the scientific literature (PMID: 28843487), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Aug 2018).
V559fs frameshift loss of function - predicted KIT V559fs results in a change in the amino acid sequence of the Kit protein beginning at aa 559 of 976, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), V559fs is predicted to lead to a loss of Kit protein function.
Q556_V559delinsH indel gain of function - predicted KIT Q556_V559delinsH results in the deletion of 4 amino acids in the juxtamembrane domain of the Kit protein from amino acids 556 to 559, combined with the insertion of a histidine (H) at the same site (PMID: 16226710). Q556_V559delinsH has not been characterized, but is predicted to activate Kit basing on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
A829P missense gain of function KIT A829P lies within the protein kinase domain of the Kit protein (UniProt.org). A829P results in constitutive phosphorylation of Kit, activation of Akt and Erk signaling, and confers acquired resistance to imatinib in culture (PMID: 23582185). Y
K818R missense unknown KIT K818R lies within the protein kinase domain of the Kit protein (UniProt.org). K818R has been identified in sequencing studies (PMID: 17566038), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558E missense unknown KIT K558E lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). K558E has been identified in sequencing studies (PMID: 19264228), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
I571_L576del deletion gain of function - predicted KIT I571_L576del results in the deletion of six amino acids in the juxtamembrane domain of the Kit protein from amino acids 571 to 576 (PMID: 12879016). I571_L576del has not been characterized, however similar Kit exon 11 deletions are activating, thus I571_L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
N655K missense gain of function - predicted KIT N655K lies within the tyrosine kinase domain 1 of the Kit protein (PMID: 17555444). N655K results in constitutive phosphorylation of Kit in cell culture in one study (PMID: 17489795) and therefore, is predicted to lead to a gain of Kit protein function.
D820Y missense gain of function KIT D820Y lies within the protein kinase domain of the Kit protein (UniProt.org). D820Yresuts in constitutive phosphorylation of Kit and is transforming in cell culture (PMID: 19035443, PMID: 11984533), and has also been identified as a secondary mutation associated with imatinib-resistance (PMID: 18488160). Y
E306* nonsense loss of function - predicted KIT E306* results in a premature truncation of the Kit protein at amino acid 306 of 976 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), E306* is predicted to lead to a loss of Kit protein function.
N320fs frameshift loss of function - predicted KIT N320fs results in a change in the amino acid sequence of the Kit protein beginning at aa 320 of 976, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), N320fs is predicted to result in a loss of Kit protein function.
D816X missense unknown KIT D816X indicates any Kit missense mutation which results in the aspartic acid (D) at amino acid 816 being replaced by a different amino acid. KIT D816 mutations are associated with resistance to Kit inhibitors (PMID: 17065430). Y
M552_V555del deletion gain of function - predicted KIT M552_V555del results in the deletion of four amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 to 555 (PMID: 16226710). M552_V555del has not been characterized, however similar Kit exon 11 deletions are activating, thus M552_V555del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
K558R missense unknown KIT K558R lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). K558R has been identified in sequencing studies (PMID: 21569090), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
Q556_V560del deletion gain of function - predicted KIT Q556_V560del results in the deletion of four amino acids in the juxtamembrane domain of the Kit protein from amino acids 556 to 560 (PMID: 16226710). Q556_V560del has not been characterized, however similar Kit exon 11 deletions are activating, thus Q556_V560del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 9797363).
V643A missense unknown KIT V643A lies within the protein kinase domain of the Kit protein (UniProt.org). V643A has been identified in sequencing studies (PMID: 19617878), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558N missense unknown KIT K558N lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). K558N has been identified in sequencing studies (PMID: 18294292), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
F584S missense unknown KIT F584S lies within the cytoplasmic domain of the Kit protein (UniProt.org). F584S has been identified in sequencing studies (PMID: 11376557), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
exon17 unknown unknown KIT exon 17 indicates an unspecified mutation has occurred in exon 17 of the KIT gene.
W557_E561del deletion gain of function - predicted KIT W557_E561del results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 561 (PMID: 16226710). W557_E561del has not been characterized, however similar Kit exon 11 deletions are activating, thus W557_E561del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
P838L missense unknown KIT P838L lies within the protein kinase domain of the Kit protein (UniProt.org). P838L has been identified in sequencing studies (PMID: 21642685) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
T417_D419delinsI deletion gain of function - predicted KIT T417_D419delinsI results in the deletion of 3 amino acids in the Ig-like C2-type domain 5 of the Kit protein from amino acids 417 to 419, combined with the insertion of an Isoleucine (I) at the same site (UniProt.org). T417_D419delinsI results in constitutive ligand-independent phosphorylation of Kit in cell culture in one study (PMID: 16015387) and therefore, is predicted to lead to a gain of Kit protein function.
Q556_V559del deletion gain of function - predicted KIT Q556_V559del results in the deletion of four amino acids in the juxtamembrane domain of the Kit protein from amino acids 556 to 559 (PMID: 16226710). Q556_V559del has not been characterized, however similar Kit exon 11 deletions are activating, thus Q556_V559del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
M537L missense unknown KIT M537L (corresponds to M541L in the canonical isoform) lies within the helical domain of the Kit protein (PMID: 16226710). M537L (M541L) is a common polymorphism that has been demonstrated to increase proliferation in the presence of ligand compared to wild-type Kit in culture (PMID: 18795925), but is not associated with tumorigenesis in the population (PMID: 16307017, PMID: 21757432) and therefore, its effect on Kit protein function is unknown.
E490K missense unknown KIT E490K lies within the Ig-like C2-type 5 domain of the Kit protein (UniProt.org). E490K has been identified in the scientific literature (PMID: 22357254) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558_Y570delinsNP indel gain of function - predicted KIT K558_Y570delinsNP results in the deletion of thirteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 570, combined with the insertion of an asparagine (N) and a proline (P) at the same site (PMID: 16226710). K558_Y570delinsNP has not been characterized, but is predicted to activate Kit basing on the effects of similar mutations (PMID: 9438854, PMID: 15365079).
L576del deletion gain of function - predicted KIT L576del results in the deletion of an amino acid in the juxtamembrane domain of the Kit protein at amino acid 576 (PMID: PMID: 9797363). L576del has not been characterized, however similar Kit exon 11 deletions are activating, thus L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
D816I missense gain of function KIT D816I lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 17555444). D816I results in constitutive phosphorylation of Kit, increased phosphorylation of Gsk3beta, activation of Stat pathways, and is transforming in cell culture (PMID: 19865100, PMID: 20484085).
V556_V560del deletion gain of function - predicted KIT V556_V560del results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 556 to 560 (PMID: 12879016). V556_V560del has not been characterized, however similar Kit exon 11 deletions are activating, thus K556_V560del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
exon11 unknown unknown KIT exon 11 indicates an unspecified mutation has occurred in exon 11 of the KIT gene.
K558delinsNP deletion unknown KIT K558delinsNP results in a deletion of lysine (K) at amino acid 558 within the juxtamembrane domain of the Kit protein, combined with the insertion of an asparagine (N) and a proline (P) at the same location (UniProt.org). K558delinsNP has been identified in the scientific literature (PMID: 11526490, PMID: 25239608) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown.
L416fs frameshift loss of function - predicted KIT L416fs results in a change in the amino acid sequence of the Kit protein beginning at aa 416 of 976, likely resulting is a premature truncation of the protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), L416fs is predicted to lead to a loss of Kit protein function.
N822K missense gain of function KIT N822K lies within the activation loop in the protein kinase domain of the Kit protein (PMID: 24205792). N822K results in constitutive activation of Kit, increased Erk1/2 and Stat3 phosphorylation, is transforming in culture (PMID: 24205792), and has been identified as a secondary mutation associated with imatinib-resistance (PMID: 18488160). Y
V560G missense gain of function KIT V560G lies within the juxtamembrane domain of the Kit protein (PMID: 9438854). V560G confers a gain of function to Kit, as indicated by constitutive phosphorylation of Kit and activation of Jak/Stat pathway in cell culture (PMID: 7691885, PMID: 23777495).
P754fs frameshift loss of function - predicted KIT P754fs results in a change in the amino acid sequence of the Kit protein beginning at aa 754 of 976 (UniProt.org), likely resulting in premature truncation of the functional protein. Due to the disruption of the protein kinase domain, P754fs is predicted to lead to a loss of Kit protein function (UniProt.org).
G565V missense unknown KIT G565V lies within the cytoplasmic domain of the Kit protein (UniProt.org). G565V has been identified in the scientific literature (PMID: 28843487), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Aug 2018).
rearrange unknown unknown KIT rearrangement indicates an unspecified rearrangement of the KIT gene.
P573L missense unknown KIT P573L lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). P573L has been identified in sequencing studies (PMID: 20180814), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558_N564del deletion gain of function - predicted KIT K558_N564del results in the deletion of seven amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 564 (PMID: 12879016). K558_N564del has not been characterized, however similar Kit exon 11 deletions are activating, thus K558_N564del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
M552_Q556del deletion gain of function - predicted KIT M552_Q556del results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 and 556 (PMID: 12879016) M552_Q556del has not been characterized, however similar Kit exon 11 deletions are activating, thus M552_Q556del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
E228* nonsense loss of function - predicted KIT E228* results in a premature truncation of the Kit protein at amino acid 228 of 976 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), E228* is predicted to lead to a loss of Kit protein function.
negative unknown loss of function KIT negative indicates a lack of the KIT gene,mRNA, and/or protein.
N564_L576del deletion gain of function - predicted KIT N564_L576del results in the deletion of thirteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 564 to 576 (PMID: 12879016). N564_L576del has not been characterized, however similar Kit exon 11 deletions are activating, thus N564_L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
W557G missense gain of function - predicted KIT W557G lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). W557G results in constitutive phosphorylation of Kit in cell culture in one study (PMID: 23567324) and therefore, is predicted to lead to a gain of Kit protein function.
V532I missense unknown KIT V532I lies within the transmembrane domain of the Kit protein (UniProt.org). V532I has been identified in the scientific literature (PMID: 25894969), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
V399I missense unknown KIT V399I lies within the Ig-like C2-type domain 4 of the Kit protein (UniProt.org). V399I has been identified in sequencing studies (PMID: 15150569), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
T274M missense unknown KIT T274M lies within the Ig-like C2-type domain 3 of the Kit protein (UniProt.org). T274M has not been characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
V560del deletion gain of function - predicted KIT V560del results in the deletion of an amino acid in the juxtamembrane domain of the Kit protein at amino acid 560 (PMID: 12879016). V560del results in transformation of cultured cells in one study (PMID: 19861435) and therefore, is predicted to lead to a gain of Kit protein function.
K550_E554del deletion gain of function - predicted KIT K550_E554del results in the deletion of 5 amino acids in the juxtamembrane domain of the Kit protein from amino acids 550 to 554 (PMID: 16226710). K550_E554del has not been characterized, however similar Kit exon 11 deletions are activating, thus K550_E554del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
T417_D419delinsY deletion gain of function KIT T417_D419delinsY results in the deletion of three amino acids in the Ig-like C2-type 5 domain of the Kit protein from amino acids 417 to 419, combined with the insertion of a Tyrosine (Y) at the same site (UniProt.org). T417_D419delinsY results in constitutive phosphorylation of Kit, activation of Akt and Stat pathways, and is transforming in culture (PMID: 20484085).
M552_E554delinsK indel gain of function - predicted KIT M552_E554delinsK results in the deletion of 3 amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 to 554, combined with the insertion of a lysine (K) at the same site (PMID: 16226710). M552_E554delinsK has not been characterized, but is predicted to lead to Kit activation based on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
P551L missense unknown KIT P551L lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). P551L has been identified in sequencing studies (PMID: 21325067), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V559del deletion gain of function KIT V559del results in the deletion of an amino acid in the juxtamembrane domain of the Kit protein at amino acid 559 (PMID: 16226710). V559del confers a gain of function on Kit, resulting in constitutive, ligand independent phosphorylation of Kit and activation of Akt in cell culture (PMID: 15236194, PMID: 22282465).
F522C missense gain of function - predicted KIT F522C lies within the transmembrane domain of the Kit protein (PMID: 15070706). F522C results in ligand independent autophosphorylation of Kit in cell culture in one study (PMID: 15070706) and therefore, is predicted to lead to a gain of Kit protein function.
D816F missense gain of function KIT D816F lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 17555444). D816F results in constitutive phosphorylation of Kit and activation of Stat3, Mapk, and Akt signaling in cultured cells (PMID: 9990072, PMID: 16397263), and also confers resistance to imatinib in culture (PMID: 16397263). Y
V560_L576del deletion gain of function - predicted KIT V560_L576del results in the deletion of seventeen amino acids in the juxtamembrane domain of the Kit protein from amino acids 560 to 576 (PMID: 12879016). V560_L576del has not been characterized, however similar Kit exon 11 deletions are activating, thus V560_L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
C443Y missense gain of function - predicted KIT C443Y lies within the Ig-like C2-type domain 5 of the Kit protein (UniProt.org). C443Y results in constitutive ligand-independent activation of Kit in cell culture in one study (PMID: 19865100) and therefore, is predicted to lead to a gain of Kit protein function.
S715del deletion unknown KIT S715del results in the deletion of an amino acid within the protein kinase domain of the Kit protein at amino acid 715 (UniProt.org). S715del has been identified in sequencing studies (PMID: 11786393), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
D816G missense gain of function KIT D816G lies within the protein kinase domain of the Kit protein (UniProt.org). D816G results in constitutive phosphorylation of Kit, is transforming in culture, and confers resistance to crizotinib (PMID: 27068398).
K642Q missense unknown KIT K642Q lies within the protein kinase domain of the Kit protein (UniProt.org). K642Q has been identified in sequencing studies (PMID: 28327988), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
W557_K558delinsC indel gain of function - predicted KIT W557_K558delinsC results in the deletion of 2 amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 558, combined with the insertion of a cystine (C) at the same site (PMID: 16226710). W557_K558delinsC has not been characterized, but is predicted to activate Kit basing on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
exon 11 del deletion gain of function KIT exon 11 deletions are in-frame deletions within the juxtamembrane domain of the Kit protein (PMID: 26349547). KIT exon 11 deletions are associated with constitutive activation of Kit (PMID: 9438854, PMID: 15365079).
N822H missense unknown KIT N822H lies within the protein kinase domain of the Kit protein (UniProt.org). N822H has been identified in sequencing studies (PMID: 11719439), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
E839K missense loss of function KIT E839K lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 17555444). E839K results in impaired Kit protein maturation, a loss of Kit phosphorylation, and dominant inhibition of activating Kit mutations in cultured cells (PMID: 9990072, PMID: 15790786).
W557S missense unknown KIT W557S lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). W557S has been identified in sequencing studies (PMID: 17438095) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, sep 2018).
W557R missense gain of function KIT W557R lies within the juxtamembrane domain of the Kit protein (PMID: 15790786). W557R has been identified in the scientific literature (PMID: 15869870) but has not been biochemically characterized and therefore, its effect on Kit protein funciton is unknown (PubMed, Sep 2018).
D579del deletion gain of function KIT D579del results in a deletion of an amino acid in the juxtamembrane domain of the Kit protein at amino acid 579 (PMID: 9797363). D579del confers a gain of function on Kit, as indicated by constitutive phosphorylation of Kit, transformation of cultured cells and tumor formation in mice (PMID: 9797363).
E53K missense unknown KIT E53K lies within the Ig-like C2-type 1 domain of the Kit protein (UniProt.org). E53K has been identified in sequencing studies (PMID: 17710669), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
I571_D579dup duplication unknown KIT I571_D579dup (also referred to as D579_H580insIDPTQLPYD) indicates the insertion of 9 duplicate amino acids, isoleucine (I)-571 through aspartic acid (D)-579, in the juxtamembrane domain of the Kit protein (PMID: 16226710). I571_D579dup has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
P577_D579del deletion gain of function - predicted KIT P577_D579del results in the deletion of three amino acids in the juxtamembrane domain of the Kit protein from amino acids 577 to 579 (UniProt.org). P577_D579del has not been characterized, however, similar Kit exon 11 deletions are activating, thus P577_D579del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
D820H missense unknown KIT D820H lies within the protein kinase domain of the Kit protein (UniProt.org). D820H has been identified in the scientific literature (PMID: 22937135, PMID: 16741525), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Jul 2018).
Y553N missense unknown KIT Y553N lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). Y553N is predicted to stabilize the active conformation of Kit by structural modeling (PMID: 23588081), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
Y553_K558del deletion gain of function - predicted KIT Y553_K558del results in the deletion of six amino acids in the juxtamembrane domain of the Kit protein from amino acids 553 to 558 (PMID: 16226710). Y553_K558del has not been characterized, however similar Kit exon 11 deletions are activating, thus Y553_K558del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 12727838).
D572Y missense unknown KIT D572Y lies within the cytoplasmic domain of the Kit protein (UniProt.org). D572Y has been identified in sequencing studies (PMID: 10485475), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
L813_A814insHIV insertion unknown KIT L813_A814insHIV results in the insertion of three amino acids in the protein kinase domain of the Kit protein between amino acids 813 and 814 (UniProt.org). L813_A814insHIV has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
V555_I571del deletion gain of function - predicted KIT V555_I571del results in the deletion of seventeen amino acids in the juxtamembrane domain of the Kit protein from amino acids 555 to 571 (PMID: 12879016). V555_I571del has not been characterized, however similar Kit exon 11 deletions are activating, thus V555_I571del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
Y568_T574del deletion gain of function - predicted KIT Y568_T574del results in the deletion of seven amino acids in the juxtamembrane domain of the Kit protein from amino acids 568 to 574 (PMID: 16226710). Y568_T574del has not been characterized, however similar Kit exon 11 deletions are activating, thus Y568_T574del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
act mut unknown gain of function KIT act mut indicates that this variant results in a gain of function in the Kit protein. However, the specific amino acid change has not been identified.
Y418_D419delinsG deletion gain of function - predicted KIT Y418_D419delinsG results in the deletion of two amino acids in the Ig-like C2-type 5 domain of the Kit protein from amino acids 418 to 419, combined with the insertion of a Glycine (G) at the same site (UniProt.org). Y418_D419delinsG has not been characterized, however similar Kit exon 8 mutations are activating, thus Y418_D419delinsG is predicted to lead to a gain of Kit protein function (PMID: 16015387, PMID: 15618474, PMID: 20484085).
L859F missense unknown KIT L859F lies within the protein kinase domain of the Kit protein (UniProt.org). L859F has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
L859S missense unknown KIT L859S lies within the protein kinase domain of the Kit protein (UniProt.org). L859S has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
T417_D419delinsRA deletion gain of function - predicted KIT T417_D419delinsRA results in the deletion of three amino acids in the extracellular domain of the Kit protein from amino acids 417 to 419, combined with the insertion of an arginine (R) and an alanine (A) at the same site (UniProt.org). T417_D419delinsRA has not been characterized, however similar Kit exon 8 mutations are activating, thus T417_D419delinsRA is predicted to lead to a gain of Kit protein function (PMID: 16015387, PMID: 15618474, PMID: 20484085).
V559D missense gain of function KIT V559D lies within the juxtamembrane domain of the Kit protein (PMID: 9438854). V559D confers a gain of function on Kit, as indicated by constitutive Kit phosphorylation, and is transforming in cell culture (PMID: 9438854, PMID: 21689725).
V559_E561del deletion gain of function - predicted KIT V559_E561del results in the deletion of three amino acids in the juxtamembrane domain of the Kit protein from amino acids 559 to 561 (PMID: 12879016). V559_E561del has not been characterized, however similar Kit exon 11 deletions are activating, thus V559_E561del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
W557_K558delinsF indel gain of function - predicted KIT W557_K558delinsF results in the deletion of 2 amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 558, combined with the insertion of a phenylalanine (F) at the same site (PMID: 16226710). KIT W557_K558delinsF has not been characterized, but is predicted to activate Kit basing on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
Y823N missense unknown KIT Y823N lies within the protein kinase domain of the Kit protein (UniProt.org). Y823N has been identified in the scientific literature (PMID: 16741525), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
G565* nonsense loss of function - predicted KIT G565* results in a premature truncation of the Kit protein at amino acid 565 of 976 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), G565* is predicted to lead to a loss of Kit protein function.
V603D missense unknown KIT V603D lies within the protein kinase domain of the Kit protein (UniProt.org). V603D has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
N566D missense unknown KIT N566D lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). N566D has been identified in sequencing studies (PMID: 16908931), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
E554_D572delinsA indel gain of function - predicted KIT E554_D572delinsA results in the deletion of 19 amino acids in the juxtamembrane domain of the Kit protein from amino acids 554 to 572, combined with the insertion of an alanine (A) at the same site (PMID: 16226710). E554_D572delinsA has not been characterized, however similar Kit exon 11 deletions are activating, thus E554_D572delinsA is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
V555_K558del deletion gain of function - predicted KIT V555_K558del results in the deletion of four amino acids in the juxtamembrane domain of the Kit protein from amino acids 555 to 558 (PMID: 12879016). V555_K558del has not been characterized, however similar Kit exon 11 deletions are activating, thus V555_K558del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
D816V missense gain of function KIT D816V lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 19865100). D816V results in constitutive phosphorylation of Kit, activation of Stat5 signaling (PMID: 19865100, PMID: 18390729), induces mastocytosis and tumor formation in mice (PMID: 21148330) and confers resistance to Kit inhibitors (PMID: 22301675, PMID: 19164557). Y
D816N missense gain of function KIT D816N lies within the protein kinase domain of the Kit protein (UniProt.org). D816N results in constitutive phosphorylation of Kit, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 11378569).
I563_L576del deletion gain of function - predicted KIT I563_L576del results in the deletion of fourteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 563 to 576 (PMID: 12879016). I563_L576del has not been characterized, however similar Kit exon 11 deletions are activating, thus I563_L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
N567_P573del deletion gain of function - predicted KIT N567_P573del results in the deletion of seven amino acids in the juxtamembrane domain of the Kit protein from amino acids 567 to 573 (PMID: 16226710). N567_P573del has not been characterized, however similar Kit exon 11 deletions are activating, thus N567_P573del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
Y568D missense unknown KIT Y568D lies within the juxtamembrane domain of the Kit protein (PMID: 23416972). Y568D has been identified in sequencing studies (PMID: 28334439, but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K509R missense unknown KIT K509R lies within the extracellular domain of the Kit protein (UniProt.org). K509R has been identified in sequencing studies (PMID: 27214377) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
N505I missense gain of function KIT N505I lies within the Ig-like C2-type domain 5 of the Kit protein (UniProt.org). N505I results in constitutive phosphorylation of Kit, activation of downstream Akt and Erk, and is transforming in cell culture (PMID: 24317392).
H697Y missense gain of function - predicted KIT H697Y lies within the protein kinase domain of the Kit protein (UniProt.org). H697Y is transforming in cultured cells in one study (PMID: 19861435) and therefore, is predicted to lead to a gain of Kit protein function.
P577_H580dup duplication unknown KIT P577_H580dup (also referred to as H580_K581insPYDH) indicates the insertion of 4 duplicate amino acids, proline (P)-577 through histidine (H)-580, in the juxtamembrane domain of the Kit protein (PMID: 16226710). P577_H580dup has not been characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
E249* nonsense loss of function - predicted KIT E249* results in a premature truncation of the Kit protein at amino acid 249 of 976 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), E249* is predicted to lead to a loss of Kit protein function.
T22A missense unknown KIT T22A does not lie within any known functional domains of the Kit protein (UniProt.org). T22A has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
W557_K558delinsCE indel gain of function - predicted KIT W557_K558delinsCE results in the deletion of 2 amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 558, combined with the insertion of a cystine (C) and a glutamic acid (E) at the same site (PMID: 16226710). W557_K558delinsCE has not been characterized, but is predicted to activate Kit basing on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
V559K missense gain of function - predicted KIT V559K lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). V559K has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018)
V654A missense unknown KIT V654A lies within the protein kinase domain of the Kit protein (UniProt.org). V654A increases proliferation of cultured cells, but is not transforming and does not result in constitutive kinase activation (PMID: 17363509), however, has been described as a secondary drug resistance mutation (PMID: 17363509, PMID: 16751810). Y
K581_W582insDPTQLPYDH insertion unknown KIT K581_W582insDPTQLPYDH results in the insertion of nine amino acids in the juxtamembrane domain of the Kit protein between amino acids 581 and 582 (PMID: 16226710). K581_W582insDPTQLPYDH has not been characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
I571V missense unknown KIT I571V lies within the cytoplasmic domain of the Kit protein (UniProt.org). I571V has been identified in sequencing studies (PMID: 24983367) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558_D572del deletion gain of function - predicted KIT K558_D572del results in the deletion of fifteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 572 (PMID: 16226710). K558_D572del has not been characterized, however similar Kit exon 11 deletions are activating, thus K558_D572del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
N567K missense unknown KIT N567K lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). N567K has been identified in sequencing studies (PMID: 15217946), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V569_L576del deletion gain of function - predicted KIT V569_L576del results in the deletion of eight amino acids in the juxtamembrane domain of the Kit protein from amino acids 569 and 576 (PMID: 12879016) V569_L576del has not been characterized, however, similar Kit exon 11 deletions are activating, thus V569_L576del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
P577S missense unknown KIT P577S lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). P577S has been identified in sequencing studies (PMID: 22261812), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V559I missense gain of function KIT V559I lies within the juxtamembrane domain of the Kit protein (PMID: 17259998). V559I confers a gain of function to Kit, as indicated by constitutive phosphorylation of Kit and increased phosphorylation of Stat1 and Mapk in cell culture (PMID: 17259998).
D572A missense gain of function - predicted KIT D572A lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). D572A results in ligand-independent phosphorylation of Kit in cell culture in one study (PMID: 19865100) and therefore, is predicted to lead to a gain of Kit protein function.
E562K missense unknown KIT E562K lies within the cytoplasmic domain of the Kit protein (UniProt.org). E562K has been identified in sequencing studies (PMID: 20861712), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V555_V560del deletion gain of function - predicted KIT V555_V560del results in the deletion of six amino acids from the juxtamembrane domain of the Kit protein from amino acids 555 to 560 (PMID: 12879016). V555_V560del has not been characterized, however similar Kit exon 11 deletions are activating, thus KV555_V560del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
P551_Q556del deletion gain of function - predicted KIT P551_Q556del results in the deletion of six amino acids in the juxtamembrane domain of the Kit protein from amino acids 551 to 556 (PMID: 16226710). P551_Q556del has not been characterized, however similar Kit exon 11 deletions are activating, thus P551_Q556del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
E561fs frameshift loss of function - predicted KIT E561fs results in a change in the amino acid sequence of the Kit protein beginning at aa 561 of 976, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E561fs is predicted to lead to a loss of Kit protein function.
K558Q missense unknown KIT K558Q lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). K558Q has been identified in the scientific literature (PMID: 19333543, PMID: 19182535), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
D572N missense unknown KIT D572N lies within the cytoplasmic domain of the Kit protein (UniProt.org). D572N has been identified in sequencing studies (PMID: 21478825), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
exon13 unknown unknown KIT exon 13 indicates an unspecified mutation has occurred in exon 13 of the KIT gene.
P577del deletion gain of function - predicted KIT P577del results in the deletion of one amino acid in the juxtamembrane domain of the Kit protein at amino acid 577 (PMID: 12879016). P577del has not been characterized, however, other Kit exon 11 deletions are activating, thus P577del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
Y553S missense unknown KIT Y553S lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). Y553S has been identified as a secondary mutation associated with imatinib-resistance (PMID: 18488160), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Jul 2018). Y
K558_G565delinsR indel gain of function - predicted KIT K558_G565delinsR results in the deletion of 9 amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 565, combined with the insertion of an arginine (R) at the same site (PMID: 16226710). K558_G565delinsR results in constitutive phosphorylation of Kit in patient-derived xenograft models in one study (PMID: 25926077) and therefore, is predicted to lead to a gain of Kit protein function.
H630Y missense unknown KIT H630Y lies within the protein kinase domain of the Kit protein (UniProt.org). H630Y has been identified in sequencing studies (PMID: 27027238), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V555_P573del deletion gain of function - predicted KIT V555_P573del results in the deletion of nineteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 555 to 573 (PMID: 12879016). V555_P573del has not been characterized, however similar Kit exon 11 deletions are activating, thus V555_P573del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
M541V missense unknown KIT M541V lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). M541V has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V852I missense unknown KIT V852I lies within the protein kinase domain of the Kit protein (UniProt.org). V852I has been identified in sequencing studies (PMID: 21642685), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558_V559del deletion gain of function - predicted KIT K558_V559del results in the deletion of two amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 559 (PMID: 12879016). K558_V559del has not been characterized, however similar Kit exon 11 deletions are activating, thus K558_V559del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
A402S missense unknown KIT A402S lies within the Ig-like C2-type domain 4 of the Kit protein (UniProt.org). A402S has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
V560dup duplication unknown KIT V560dup indicates the insertion of the duplicate amino acid, valine (V)-560, in the juxtamembrane domain of the Kit protein (PMID: 16226710). V560dup has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
D60N missense unknown KIT D60N lies within the fIg-like C2-type domain 1 of the Kit protein (UniProt.org). The functional effect of D60N is conflicting, as it results in activation of Jak-Stat signaling and increased proliferation, but also reduced ligand binding to Kit and decreased Akt and Erk signaling in culture (PMID: 24211109).
M552L missense unknown KIT M552L lies within the juxtamembrane domain of the Kit protein (PMID: 12879016). M552L has been identified in sequencing studies (PMID: 12759497), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
S197* nonsense loss of function - predicted KIT S197* results in a premature truncation of the Kit protein at amino acid 197 of 976 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), S197* is predicted to lead to a loss of Kit protein function.
M552_W557del deletion gain of function - predicted KIT M552_W557del results in the deletion of six amino acids in the juxtamembrane domain of the Kit protein from amino acids 552 and 557 (PMID: 12879016). M552_W557del has not been characterized, however similar Kit exon 11 deletions are activating, thus M552_W557del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
positive none unknown KIT positive indicates the presence of the KIT gene, mRNA, and/or protein.
Y553_Q556del deletion gain of function KIT Y553_Q556del results in the deletion of four amino acids in the juxtamembrane domain of the Kit protein from amino acids 553 to 556 (PMID: 16226710). Y553_Q556del confers a gain of function on Kit, as indicated by autophosphorylation of Kit, activation of Stat3 and Akt (PMID: 15690055), and increased Hmgb1 expression in patient samples (PMID: 12727838).
Y823C missense unknown KIT Y823C lies within the protein kinase domain of the Kit protein (UniProt.org). Y823C has been identified in sequencing studies (PMID: 14695343), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558_Y570delinsN indel gain of function - predicted KIT K558_Y570delinsN results in the deletion of thirteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 570, combined with the insertion of an asparagine (N) at the same site (PMID: 16226710). K558_Y570delinsN has not been characterized, but is predicted to activate Kit basing on the effects of similar mutations (PMID: 9438854, PMID: 15365079).
Y553_E561delinsLK indel gain of function - predicted KIT Y553_E561delinsLK results in the deletion of nine amino acids in the juxtamembrane domain of the Kit protein from amino acids 553 to 561, combined with the insertion of a leucine (L) and a lysine (K) at the same site (PMID: 16226710). Y553_E561delinsLK has not been characterized, but is predicted to activate Kit basing on the effects of similar Kit exon 11 mutations (PMID: 9438854, PMID: 15365079).
V560D missense gain of function KIT V560D lies within the juxtamembrane domain of the Kit protein (PMID: 19164557). V560D confers a gain of function on Kit, as indicated by constitutive phosphorylation of Kit in cell culture (PMID: 16954519, PMID: 20633291).
N463S missense unknown KIT N463S lies within the Ig-like C2-type domain 5 of the Kit protein (UniProt.org). N463S has been identified in sequencing studies (PMID: 21642685), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V825A missense unknown KIT V825A lies within the protein kinase domain of the Kit protein (UniProt.org). V825A cooperates with an activation RUNX1-ETO fusion protein to promote cell growth in one study (PMID: 24897507), but has not been characterized individually and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
K558_V560del deletion gain of function - predicted KIT K558_V560del results in the deletion of three amino acids in the juxtamembrane domain of the Kit protein from amino acids 558 to 560 (PMID: 12879016). K558_V560del has not been characterized, however similar Kit exon 11 deletions are activating, thus K558_V560del is predicted to lead to a gain of function (PMID: 9438854, PMID: 15365079).
V556_T574del deletion gain of function - predicted KIT V556_T574del results in the deletion of 19 amino acids in the juxtamembrane domain of the Kit protein from amino acids 556 to 574 (PMID: 16226710). V556_T574del has not been characterized, however similar Kit exon 11 deletions are activating, thus V556_T574del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
Y578C missense gain of function - predicted KIT Y578C lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). Y578C results in constitutive phosphorylation of Kit in cell culture in one study (PMID: 23567324) and therefore, is predicted to lead to a gain of Kit protein function.
E554_K558del deletion gain of function - predicted KIT E554_K558del results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 554 to 558 (PMID: 12879016). E554_K558del has not been characterized, however similar Kit exon 11 deletions are activating, thus E554_K558del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
G779C missense unknown KIT G779C lies within the protein kinase domain of the Kit protein (UniProt.org). G779C has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
V530I missense gain of function KIT V530I lies within the transmembrane domain of the Kit protein (PMID: 16081693). V530I confers a gain of function on Kit, as indicated by constitutive phosphorylation of Kit and activation of Akt, Mapk, Stat3, and Stat5 in cell culture (PMID: 16081693).
C809G missense unknown KIT C809G lies within the protein kinase domain of the Kit protein (UniProt.org). C809G has been identified in sequencing studies (PMID: 18452195), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
exon14 unknown unknown KIT exon 14 indicates an unspecified mutation has occurred in exon 14 of the KIT gene.
G51D missense unknown KIT G51D lies within the Ig-like C2-type domain 1 of the Kit protein (UniProt.org). G51D has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
N564_Y578del deletion gain of function - predicted KIT N564_Y578del results in the deletion of fifteen amino acids in the juxtamembrane domain of the Kit protein from amino acids 564 to 578 (PMID: 12879016). N564_Y578del has not been characterized, however similar Kit exon 11 deletions are activating, thus N564_Y578del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 15365079).
P551H missense unknown KIT P551H lies within the juxtamembrane domain of the Kit protein (PMID: 16226710). P551H has been identified in sequencing studies (PMID: 17200352) but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
P551_V555del deletion gain of function KIT P551_V555deI results in the deletion of five amino acids in the juxtamembrane domain of the Kit protein from amino acids 551 to 555 (PMID: 9438854). P551_V555del confers a gain of function on Kit, as indicated by constitutive Kit phosphorylation, and is transforming in cell culture (PMID: 9438854).
Y823H missense unknown KIT Y823H lies within the protein kinase domain of the Kit protein (UniProt.org). Y823H has been identified in sequencing studies (PMID: 23014346), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Sep 2018).
D816Y missense gain of function KIT D816Y lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 21640708). D816Y results in constitutive phosphorylation of Kit, activation of Akt and Mapk pathways in cultured cells (PMID: 21640708, PMID: 16397263), and confers resistance to imatinib in culture (PMID: 16397263). Y
R796G missense loss of function KIT R796G lies within the protein kinase domain of the Kit protein (UniProt.org). R796G confers a loss of function on Kit as indicated by lack of autophosphorylation, loss of ligand-induced phosphorylation of Kit in cultured cells (PMID: 20824047).
W557_V560del deletion gain of function - predicted KIT W557_V560del results in the deletion of four amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 560 (PMID: 16226710). W557_V560del has not been characterized, however similar Kit exon 11 deletions are activating, thus W557_V560del is predicted to lead to a gain of Kit protein function (PMID: 9438854, PMID: 9797363).
T670E missense unknown KIT T670E lies within the protein kinase domain of the Kit protein (UniProt.org). T670E has been identified in the scientific literature (PMID: 19834613), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2018).
D820V missense unknown KIT D820V lies within the protein kinase domain of the Kit protein (UniProt.org). D820V has been identified as a secondary mutation associated with imatinib?resistant (PMID: 18294292), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Jul 2018). Y
N822I missense gain of function KIT N822I lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 17555444). N822I results in constitutive Kit phosphorylation, is transforming in cell culture, and confers resistance to imatinib (PMID: 21689725). Y
G510C missense unknown KIT G510C lies within the extracellular domain of the Kit protein (UniProt.org). G510C has not been characterized in the scientific literature and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
S476I missense gain of function KIT S476I lies within the extracellular domain of the Kit protein (UniProt.org). S476I confers a gain of function on Kit, as indicated by constitutive phosphorylation of Kit in cell culture (PMID: 19865100, PMID: 30094412).
W557_K558del deletion gain of function KIT W557_K558del results in the deletion of 2 amino acids in the juxtamembrane domain of the Kit protein from amino acids 557 to 558 (PMID: 12918066). W557_K558del results in constitutive activation of Kit and increased Erk phosphorylation, and leads to increased invasiveness and expression of ETV1 in cell culture (PMID: 25239608, PMID: 26936919).
S628N missense gain of function KIT S628N lies within the protein kinase domain of the Kit protein (UniProt.org). S628N results in constitutive Kit phosphorylation and activation of downstream Stat3, Akt and Erk1/2, and is transforming in cell culture (PMID: 25317746).
R804W missense unknown KIT R804W lies within the activation loop in the kinase domain of the Kit protein (PMID: 21478825). R804W is predicted to have lower binding affinity for imatinib relative to wild-type Kit protein (PMID: 20140688), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Mar 2018).
Molecular Profile Protein Effect Treatment Approaches
KIT V559C unknown
KIT V559_V560delinsS gain of function - predicted KIT Inhibitor
KIT K558_V560del KIT W557C
KIT W557C unknown KIT Inhibitor
KIT W557C KIT Y578C
KIT L576F unknown
KIT V559_V560del gain of function KIT Inhibitor
KIT V825I unknown
KIT K642E gain of function KIT Inhibitor
KIT Q556_K558del gain of function - predicted KIT Inhibitor
KIT L576P KIT W557R
KIT L576P gain of function KIT Inhibitor
KIT G812V unknown
RUNX1-RUNX1T1 KIT mut
KIT mutant unknown
KIT P551_V555delinsTL gain of function - predicted KIT Inhibitor
KIT E490* loss of function - predicted
KIT wild-type no effect
KIT K550_W557del gain of function - predicted KIT Inhibitor
KIT M552_D572del gain of function - predicted KIT Inhibitor
KIT Y553C unknown
KIT D820N unknown
KIT Y553_W557del gain of function - predicted KIT Inhibitor
KIT N80S unknown
KIT Y570H unknown
KIT V556_L576del gain of function - predicted KIT Inhibitor
KIT D820E unknown
KIT A502_Y503dup KIT D820E
KIT R634L unknown
KIT S501_A502dup gain of function - predicted KIT Inhibitor
KIT D816E KIT Y570_L576del PTEN T321fs
KIT Y570_L576del gain of function - predicted KIT Inhibitor
KIT N822Y gain of function - predicted KIT Inhibitor
KIT M552_Y553del gain of function - predicted KIT Inhibitor
KIT D820A unknown
KIT D820A KIT V560D
KIT W557_K558del KIT D820A
KIT M552_E554del gain of function - predicted KIT Inhibitor
KIT Q556_W557del gain of function - predicted KIT Inhibitor
KIT P551_M552delinsL gain of function - predicted KIT Inhibitor
KIT V555_E562del gain of function - predicted KIT Inhibitor
KIT E554K unknown
KIT V560E gain of function - predicted KIT Inhibitor
KIT exon 9 unknown
KIT W557_K558delinsE gain of function - predicted KIT Inhibitor
KIT E695* loss of function - predicted
KIT T417_Y418delinsH gain of function - predicted KIT Inhibitor
KIT T632I unknown
KIT W557_V559delinsF unknown
KIT V559G gain of function - predicted KIT Inhibitor
KIT W557Lfs*5 loss of function - predicted
KIT P577del KIT W557Lfs*5 KIT D820G
KIT D820G KIT V559D
KIT V555_L576del KIT D820G KIT D820Y
KIT D820G unknown KIT Inhibitor
KIT W557_K558del KIT D820G
KIT K558* loss of function - predicted
KIT D52N unknown
KIT K550_K558del gain of function KIT Inhibitor
KIT Y578_D579del gain of function - predicted KIT Inhibitor
KIT W557del gain of function - predicted KIT Inhibitor
KIT R634W gain of function KIT Inhibitor
KIT V555_L576del gain of function - predicted
KIT D816E unknown KIT Inhibitor Avapritinib
KIT V560_Y578del KIT D816E
KIT D816E KIT D820V
KIT K558_Y570delinsR gain of function - predicted KIT Inhibitor
KIT W557F unknown
KIT K558_V559insNP unknown
KIT V555_Q556del gain of function - predicted KIT Inhibitor
KIT V559_G565del gain of function - predicted KIT Inhibitor
KIT M552_V559delinsI gain of function - predicted KIT Inhibitor
KIT I653T unknown
KIT P577_E583dup unknown
KIT K550_V559del gain of function - predicted KIT Inhibitor
KIT V559A gain of function KIT Inhibitor
KIT T670I KIT V559D
KIT exon 11 KIT T670I
KIT T670I gain of function KIT Inhibitor
KIT W557_K558del KIT T670I
KIT V560_Y578del KIT T670I
KIT T670I KIT V560D
KIT Y823D gain of function KIT Inhibitor
KIT W557_K558del KIT Y823D
KIT V559D KIT Y823D
KIT M552_K558del gain of function - predicted KIT Inhibitor
KIT V555_V559del gain of function - predicted KIT Inhibitor
KIT D816A unknown Avapritinib
KIT L813_V824dup unknown
KIT A502_Y503dup gain of function KIT Inhibitor
KIT A502_Y503dup KIT N822K
KIT A502_Y503dup PDGFRA H687Y
KIT K509I gain of function KIT Inhibitor
KIT S709F unknown
KIT F811L unknown
KIT C443S unknown
KIT V555I unknown
KIT K550_V555delinsI gain of function - predicted KIT Inhibitor
KIT S501_A502insSAY gain of function - predicted KIT Inhibitor
KIT amp PDGFRA amp
ROS1 fusion KDR amp KIT amp PDGFRA amp
KIT amp no effect KIT Inhibitor
KIT E561K unknown
KIT V560_Y578del KIT A829P
KIT V560_Y578del gain of function - predicted KIT Inhibitor
KIT A794E unknown
KIT T670S unknown
KIT D419del gain of function KIT Inhibitor
KIT L576_P585dup unknown
KIT W557_V559del gain of function - predicted KIT Inhibitor
KIT G387R unknown
KIT L576R unknown
KIT P551_W557delinsL gain of function - predicted KIT Inhibitor
KIT T67S unknown
KIT W582* loss of function - predicted
KIT M552_V559del gain of function - predicted KIT Inhibitor
KIT Y418_D419delinsS gain of function - predicted KIT Inhibitor
KIT P551_E554del gain of function - predicted KIT Inhibitor
KIT V559_T574del gain of function - predicted KIT Inhibitor
KIT W853* unknown
KIT M541L unknown
KIT V560del KIT over exp
KIT over exp no effect
KIT V560A gain of function - predicted KIT Inhibitor
KIT D816H gain of function Avapritinib Dasatinib
KIT W557_K558del KIT D816H
KIT K558_E562del gain of function - predicted KIT Inhibitor
KIT L631F unknown
KIT V559fs loss of function - predicted
KIT Q556_V559delinsH gain of function - predicted KIT Inhibitor
KIT A829P KIT V559D
KIT A829P gain of function KIT Inhibitor
KIT W557_K558del KIT A829P
KIT exon 11 KIT A829P
KIT K818R unknown
KIT K558E unknown
KIT I571_L576del gain of function - predicted KIT Inhibitor
KIT N655K gain of function - predicted KIT Inhibitor
KIT D820Y KIT V559D
KIT D820Y gain of function KIT Inhibitor
KIT Y553S KIT V556_T574del KIT D820Y
KIT E306* loss of function - predicted
KIT N320fs loss of function - predicted
KIT D816X unknown
KIT M552_V555del gain of function - predicted KIT Inhibitor
KIT K558R unknown
KIT Q556_V560del gain of function - predicted KIT Inhibitor
KIT V643A unknown
KIT K558N unknown
KIT F584S unknown
KIT exon 11 KIT exon 17
KIT exon 17 unknown
KIT W557_E561del gain of function - predicted KIT Inhibitor
KIT P838L unknown
KIT T417_D419delinsI gain of function - predicted KIT Inhibitor
KIT Q556_V559del gain of function - predicted KIT Inhibitor
KIT M537L unknown
KIT E490K unknown KIT Inhibitor
KIT K558_Y570delinsNP gain of function - predicted KIT Inhibitor
KIT L576del gain of function - predicted KIT Inhibitor
KIT D816I gain of function KIT Inhibitor Avapritinib
KIT V556_V560del gain of function - predicted KIT Inhibitor
KIT exon 11 KIT V654A
KIT exon 11 unknown
KIT K558delinsNP unknown KIT Inhibitor
KIT L416fs loss of function - predicted
KIT N822K gain of function KIT Inhibitor Avapritinib
KIT N822K KIT V559D
KIT W557_K558del KIT N822K
KIT W557_K558delinsCE KIT N822K
KIT V569_L576del KIT V654A KIT N822K
KIT D816V KIT V560G
KIT V560G gain of function KIT Inhibitor
KIT P754fs loss of function - predicted
KIT G565V unknown
KIT rearrange unknown
KIT P573L unknown
KIT K558_N564del gain of function - predicted KIT Inhibitor
KIT M552_Q556del gain of function - predicted KIT Inhibitor
KIT E228* loss of function - predicted
KIT negative loss of function
KIT N564_L576del gain of function - predicted KIT Inhibitor
KIT W557G gain of function - predicted KIT Inhibitor
KIT V532I unknown
KIT V399I unknown
KIT T274M unknown
KIT V560del KIT V654A
KIT V560del gain of function - predicted KIT Inhibitor
KIT K550_E554del gain of function - predicted KIT Inhibitor
KIT T417_D419delinsY gain of function KIT Inhibitor
KIT M552_E554delinsK gain of function - predicted KIT Inhibitor
KIT P551L unknown
KIT V559del gain of function KIT Inhibitor
KIT F522C gain of function - predicted KIT Inhibitor
KIT D816F gain of function KIT Inhibitor Avapritinib
KIT V560_L576del gain of function - predicted KIT Inhibitor
KIT V560_L576del KIT V654A
KIT C443Y gain of function - predicted KIT Inhibitor
KIT S715del unknown
KIT W557_K558del KIT D816G
KIT D816G ROS1 fusion
KIT D816G gain of function KIT Inhibitor Avapritinib
KIT K642Q unknown
KIT W557_K558delinsC gain of function - predicted KIT Inhibitor
KIT exon 11 del gain of function KIT Inhibitor
KIT N822H unknown
KIT E839K loss of function
KIT W557S unknown KIT Inhibitor
KIT W557R gain of function KIT Inhibitor
KIT D579del gain of function KIT Inhibitor
KIT E53K unknown
KIT I571_D579dup unknown
KIT P577_D579del gain of function - predicted KIT Inhibitor
KIT D820H unknown KIT Inhibitor
KIT Y553N unknown KIT Inhibitor
KIT Y553_K558del gain of function - predicted KIT Inhibitor
KIT D572Y unknown
KIT L813_A814insHIV unknown
KIT V555_I571del gain of function - predicted KIT Inhibitor
KIT Y568_T574del gain of function - predicted KIT Inhibitor
KIT act mut gain of function KIT Inhibitor
KIT Y418_D419delinsG gain of function - predicted KIT Inhibitor
KIT L859F unknown
KIT L859S unknown
KIT T417_D419delinsRA gain of function - predicted KIT Inhibitor
KIT V559D KIT V654A
KIT V559D gain of function KIT Inhibitor
KIT V559_E561del gain of function - predicted KIT Inhibitor
KIT W557_K558delinsF gain of function - predicted KIT Inhibitor
KIT Y823N unknown KIT Inhibitor
KIT G565* loss of function - predicted
KIT V603D unknown
KIT N566D unknown
KIT E554_D572delinsA gain of function - predicted KIT Inhibitor
KIT V555_K558del gain of function - predicted KIT Inhibitor
KIT D816V gain of function Avapritinib Dasatinib
KIT D816V NRAS Q61R
KIT D816N gain of function KIT Inhibitor Avapritinib
KIT I563_L576del gain of function - predicted KIT Inhibitor
KIT N567_P573del gain of function - predicted KIT Inhibitor
KIT Y568D unknown
KIT K509R unknown
KIT N505I gain of function KIT Inhibitor
KIT H697Y gain of function - predicted KIT Inhibitor
KIT P577_H580dup unknown
KIT E249* loss of function - predicted
KIT T22A unknown
KIT W557_K558delinsCE gain of function - predicted
KIT V559K gain of function - predicted KIT Inhibitor
KIT V654A unknown
KIT K558_V560del KIT V654A
KIT V560D KIT V654A
KIT W557_K558del KIT V654A
KIT K581_W582insDPTQLPYDH unknown
KIT I571V unknown
KIT K558_D572del gain of function - predicted KIT Inhibitor
KIT N567K unknown
KIT V569_L576del gain of function - predicted KIT Inhibitor
KIT P577S unknown
KIT V559I gain of function KIT Inhibitor
KIT D572A gain of function - predicted KIT Inhibitor
KIT E562K unknown
KIT V555_V560del gain of function - predicted KIT Inhibitor
KIT P551_Q556del gain of function - predicted KIT Inhibitor
KIT E561fs loss of function - predicted
KIT K558Q unknown
KIT D572N unknown
KIT exon 13 unknown
KIT P577del gain of function - predicted KIT Inhibitor
KIT K558_G565delinsR gain of function - predicted KIT Inhibitor
KIT H630Y unknown
KIT V555_P573del gain of function - predicted KIT Inhibitor
KIT M541V unknown
KIT V852I unknown
KIT K558_V559del gain of function - predicted KIT Inhibitor
KIT A402S unknown
KIT V560dup unknown
KIT D60N unknown KIT Inhibitor
KIT M552L unknown
KIT S197* loss of function - predicted
KIT M552_W557del gain of function - predicted KIT Inhibitor
KIT positive unknown
BRAF wild-type KIT positive
KIT Y553_Q556del gain of function KIT Inhibitor
KIT Y823C unknown
KIT K558_Y570delinsN gain of function - predicted KIT Inhibitor
KIT Y553_E561delinsLK gain of function - predicted KIT Inhibitor
KIT V560D gain of function KIT Inhibitor
KIT N463S unknown
KIT V825A unknown KIT Inhibitor
KIT K558_V560del gain of function - predicted KIT Inhibitor
KIT V556_T574del gain of function - predicted
KIT Y578C gain of function - predicted KIT Inhibitor
KIT E554_K558del gain of function - predicted KIT Inhibitor
KIT G779C unknown
KIT V530I gain of function KIT Inhibitor
KIT C809G unknown
KIT exon 14 unknown
KIT G51D unknown
KIT N564_Y578del gain of function - predicted KIT Inhibitor
KIT P551H unknown
KIT P551_V555del gain of function KIT Inhibitor
KIT Y823H unknown
KIT D816Y gain of function KIT Inhibitor Avapritinib
KIT R796G loss of function
KIT W557_V560del gain of function - predicted KIT Inhibitor
KIT T670E unknown
KIT D820V unknown KIT Inhibitor
KIT N822I gain of function KIT Inhibitor
KIT G510C unknown
KIT S476I gain of function KIT Inhibitor
KIT S476I MET R988C
KIT W557_K558del gain of function KIT Inhibitor
KIT S628N gain of function KIT Inhibitor
KIT R804W unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT K558_V560del KIT W557C gastrointestinal stromal tumor sensitive Ponatinib Clinical Study Actionable In a clinical study, a GIST patient harboring KIT K558_V560del and KIT W557C, resistant to Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib), demonstrated sensitivity when treated with Iclusig (ponatinib), which resulted in a radiologic response and stabilization for six months (PMID: 25239608). 25239608
KIT W557C KIT Y578C Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing both KIT W557C and KIT Y578C in culture (PMID: 23567324). 23567324
KIT V559_V560del Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Gleevec (imatinib), demonstrating decreased cell proliferation in culture (PMID: 24205792). 24205792
KIT V559_V560del Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Sutent (sunitinib), demonstrating decreased cell proliferation in culture (PMID: 24205792). 24205792
KIT V559_V560del Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Flumatinib, demonstrating decreased cell proliferation in culture (PMID: 24205792). 24205792
KIT K642E vulvar melanoma predicted - sensitive Imatinib Clinical Study Actionable In a clinical case report, Gleevec (imatinib mesylate) treatment resulted in partial response in a patient with recurrent vulval melanoma harboring KIT K642E, reduced tumor mass by 35% (PMID: 20372153). 20372153
KIT K642E gastrointestinal stromal tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line harboring KIT K642E demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). 25239608
KIT K642E gastrointestinal stromal tumor sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 21170960). 21170960
KIT K642E gastrointestinal stromal tumor sensitive BGJ398 + Imatinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Gleevec (imatinib mesylate) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 25673643). 25673643
KIT K642E melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT K642E demonstrating a partial response and a progression free survival of 5.8 months and overall survival of 18.6 months (PMID: 28327988). 28327988
KIT L576P KIT W557R melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient co-harboring KIT L576P and KIT W557R demonstrating a partial response and a progression free survival of 5.3 months and overall survival of 14.7 months when treated with Tasigna (nilotinib) (PMID: 28327988). 28327988
KIT L576P melanoma no benefit Imatinib Clinical Study Actionable In a clinical case report, Gleevec (imatinib mesylate) treatment resulted in initial tumor reduction followed by disease progression in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153). 20372153
KIT L576P melanoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT L576P in culture (PMID: 29035277). 29035277
KIT L576P melanoma sensitive Dasatinib Clinical Study Actionable In two clinical case studies, patients with Gleevec (imatinib)-melanoma that harboring KIT L576P demonstrated initial clinical benefit following treatment with Sprycel (dasatinib), however progressed after 3-4 months of treatment (PMID: 19671763). 19671763
KIT L576P melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including three melanoma patients harboring KIT L576P demonstrating a partial response (PMID: 28327988). 28327988
KIT L576P melanoma sensitive SEL201 Preclinical - Cell line xenograft Actionable In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cells harboring KIT L576P in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). 29035277
KIT L576P melanoma sensitive Bevacizumab + Sorafenib Clinical Study Actionable In a clinical case study, a melanoma patient harboring KIT L576P demonstrated sensitivity to the combination treatment of Nexavar (sorafenib) and Avastin (bevacizumab), resulting in a partial response for 8 months (PMID: 25363205). 25363205
RUNX1-RUNX1T1 KIT mut acute myeloid leukemia not applicable N/A Clinical Study Prognostic In clinical analyses, coincident KIT mutations were associated with higher relapse rate and decreased overall survival in acute myeloid leukemia patients with RUNX1-RUNX1T1 fusions (PMID: 18648004, PMID: 16384925, PMID: 25111512). 25111512 16384925 18648004
KIT mutant gastrointestinal stromal tumor sensitive BGJ398 + Imatinib Preclinical - Pdx Actionable In a preclinical study, BGJ398 and Gleevec (imatinib mesylate) 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 predicted - sensitive Avapritinib Phase I Actionable In a Phase I (NAVIGATOR) trial, Avapritinib (BLU-285) 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 DCC-2618 Phase I Actionable In a Phase I trial, DCC-2618 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 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 P551_V555delinsTL gastrointestinal stromal tumor sensitive Sorafenib Preclinical - Pdx Actionable In a preclinical study, Nexavar (sorafenib) inhibited Erk signaling, induced apoptosis, resulted in tumor growth inhibition in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT P551_V555delinsTL (PMID: 19139124). 19139124
KIT wild-type acute myeloid leukemia sensitive BPR1J373 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KIT wild-type was sensitive to BPR1J373 in culture, demonstrating apoptotic induction and inhibition of cell proliferation (PMID: 27512117). 27512117
KIT wild-type megakaryocytic leukemia decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, KIT wild-type megakaryocytic leukemia cells were less sensitive to BLU-285 compared to cells harboring KIT mutations in culture (PMID: 29093181). 29093181
KIT K550_W557del Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K550_W557del Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K550_W557del Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K550_W557del Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Stivarga (regorafenib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT D820N gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical case study, KIT D820N was identified as a secondary mutation in the metastatic lesions from a gastrointestinal stromal tumor patient whose disease progressed on Gleevec (imatinib mesylate) (PMID: 18628470). 18628470
KIT D820E thymic carcinoma sensitive Sorafenib Clinical Study Actionable In a clinical case report, a patient with metastatic thymic carcinoma harboring KIT D820E demonstrated a partial response to treatment with Nexavar (sorafenib) (PMID: 19461405). 19461405
KIT D820E Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT D820E demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT A502_Y503dup KIT D820E gastrointestinal stromal tumor predicted - resistant Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (26.2%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT A502_Y503dup KIT D820E gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (7.4%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor resistant Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) demonstrated limited inhibition of Kit, Erk, and Mtor signaling and resulted in minimal (22.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor sensitive Imatinib mesylate + LY294002 Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) in combination with LY394002 resulted in enhanced tumor growth inhibition compared to monotherapy in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) inhibited Kit, Erk, and Mtor signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT D820A KIT V560D gastrointestinal stromal tumor resistant Sunitinib Preclinical Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560D and KIT D820A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 18955458). 18955458
KIT D820A KIT V560D gastrointestinal stromal tumor resistant Imatinib Clinical Study Actionable In a clinical study, KIT D820A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT V560D mutation, who developed resistance to Gleevec (imatinib mesylate) (PMID: 16954519). 16954519
KIT D820A KIT V560D gastrointestinal stromal tumor resistant Imatinib Preclinical Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560D and KIT D820A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16954519). 16954519
KIT W557_K558del KIT D820A Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820A Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing W557_K558del and KIT D820A were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820A Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820A Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT exon 9 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 exon 9 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 exon 9 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 exon 9 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 exon 9 gastrointestinal stromal tumor predicted - sensitive Sunitinib Clinical Study 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 W557_V559delinsF gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, BLU-285 treatment resulted in tumor regression in patient-derived xenograft models of gastrointestinal stromal tumor harboring KIT W557_V559delinsF (PMID: 29093181). 29093181
KIT P577del KIT W557Lfs*5 KIT D820G gastrointestinal stromal tumor sensitive PLX9486 Preclinical - Pdx Actionable In a preclinical study, PLX9486 treatment decreased Mapk and Kit downstream signaling, resulted in tumor volume stabilization in patient-derived xenograft (PDX) models of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (18th Annual BSMO Meeting, Feb 2016, abstract O5). detail...
KIT P577del KIT W557Lfs*5 KIT D820G gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT mutations, P577del, W557Lfs*5, and D820G, demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 27777285). 27777285
KIT P577del KIT W557Lfs*5 KIT D820G gastrointestinal stromal tumor sensitive Cabozantinib Preclinical - Pdx Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) slowed tumor growth and decreased mitotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT mutations, P577del, W557Lfs*5, and D820G (PMID: 27777285). 27777285
KIT D820G KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D820G and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT V555_L576del KIT D820G KIT D820Y gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT D820G and KIT D820Y were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V555_L576del, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT W557_K558del KIT D820G Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820G Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820G Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820G Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT V560_Y578del KIT D816E gastrointestinal stromal tumor decreased response Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT D816E demonstrated a decreased response to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT D816E KIT D820V gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT D816E and D820V were identified as secondary mutations in a patient with gastrointestinal stromal tumor who developed resistance to Gleevec (imatinib mesylate)(PMID: 18294292). 18294292
KIT V559A melanoma predicted - sensitive Imatinib Clinical Study Actionable In a clinical case study, Gleevec (imatinib) treatment in a patient with metastatic melanoma resulted in regression of the lung metastasis, which harbored KIT V559A, however, neither the primary tumor or lymph node metastasis responded, which had wild-type KIT (PMID: 19812602). 19812602
KIT V559A gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT V559A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT V559A melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V559A demonstrating a partial response and progression free survival of 19.4 months and overall survival of 32.9 months (PMID: 28327988). 28327988
KIT T670I KIT V559D Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V559D and KIT T670I were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT exon 11 KIT T670I gastrointestinal stromal tumor predicted - sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) inhibited Kit signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT exon 11 KIT T670I gastrointestinal stromal tumor predicted - sensitive Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) inhibited Kit signaling, resulted in 86.7% tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT exon 11 KIT T670I gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk signaling and resulted in limited (53.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT T670I melanoma resistant Dasatinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Sprycel (dasatinib) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT T670I melanoma sensitive Sunitinib Preclinical Actionable In a preclinical study, Sutent (sunitinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT T670I (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT T670I melanoma resistant Imatinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT T670I Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT T670I demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT T670I gastrointestinal stromal tumor resistant Imatinib Clinical Study Actionable In a clinical case report, a patient with a gastrointestinal stromal tumor developed disease progression while being treated with Gleevec (imatinib), demonstrating a KIT T670I mutation in the progressive lesion (PMID: 15236194). 15236194
KIT T670I melanoma resistant Nilotinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Tasigna (nilotinib) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT W557_K558del KIT T670I Advanced Solid Tumor no benefit Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Nilotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Tasigna (nilotinib) in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Sprycel (dasatinib) in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation and induced apoptosis of transformed cells expressing a KIT W557_K558del/T670I double mutation in culture (PMID: 17699867). 17699867
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) (PMID: 25239608). 25239608
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT T670I KIT V560D Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/T670I double mutation in culture (PMID: 20633291). 20633291
KIT T670I KIT V560D Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V560D and KIT T670I were resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT Y823D Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT Y823D in culture (PMID: 20633291). 20633291
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib mesylate)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and Y823D (PMID: 29093181). 29093181
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive DCC-2618 Preclinical - Pdx Actionable In a preclinical study, DCC-2618 induced tumor regression in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Ponatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT W557_K558del and KIT Y823D demonstrated sensitivity to Iclusig (ponatinib) in a PDX model, resulting in complete tumor regression (PMID: 25239608). 25239608
KIT V559D KIT Y823D Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT Y823D and KIT V559D were insensitive to Sutent (sunitinib) in culture and in mouse models (PMID: 24205792). 24205792
KIT V559D KIT Y823D Advanced Solid Tumor sensitive Flumatinib Preclinical Actionable In a preclinical study, Flumatinib treatment in transformed cells co-expressing KIT N822K and KIT V559D demonstrated decreased cell proliferation and inhibition of Kit, Erk 1/2, and Stat3 phosphorylation in culture, and led to improved survival in mouse models (PMID: 24205792). 24205792
KIT V559D KIT Y823D Advanced Solid Tumor no benefit Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) treatment in a mouse model with cells expressing KIT V559D and KIT Y823D resulted in shortened survival (PMID: 24205792). 24205792
KIT M552_K558del gastrointestinal stromal tumor resistant Ponatinib Clinical Study Actionable In a clinical study, a GIST patient harboring KIT M552_K558del, resistant to multiple tyrosine kinase inhibitors, demonstrated resistance to Iclusig (ponatinib) treatment as indicated by disease progression after 4 weeks of treatment (PMID: 25239608). 25239608
KIT A502_Y503dup Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup gastrointestinal stromal tumor sensitive Cabozantinib Preclinical - Pdx Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) resulted in decreased tumor volume and reduced mitotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup (PMID: 27777285). 27777285
KIT A502_Y503dup Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Gleevec (imatinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup demonstrated resistance to treatment with Gleevec (imatinib), resulting in increased tumor volume (PMID: 27777285). 27777285
KIT A502_Y503dup gastrointestinal stromal tumor predicted - sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) did not significantly inhibit Kit, Erk, or Mtor signaling, but resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT A502_Y503dup KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT N822K was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT A502_Y503dup, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT A502_Y503dup PDGFRA H687Y gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, PDGFRA H687Y was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring primary KIT A502_Y503dup, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT C443S mucosal melanoma sensitive Imatinib Clinical Study Actionable In a case report study, a patient with mucosal melanoma harboring KIT C443S demonstrated a substantial response to Gleevec (imatinib) in the first two weeks and then developed progression at 15 weeks (PMID: 25003536). 25003536
KIT amp PDGFRA amp glioblastoma multiforme sensitive DCC-2618 Phase I Actionable In a Phase I trial, DCC-2618 demonstrated preliminary safety and efficacy in patients with advanced solid tumors, including a partial response in a glioblastoma multiforme patient harboring KIT and PDGFRA amplification (EORTC-NCI-AACR 2016, Abs 7LBA). detail...
ROS1 fusion KDR amp KIT amp PDGFRA amp non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of KIT, KDR, and PDGFRA (PMID: 29636358). 29636358
KIT V560_Y578del KIT A829P gastrointestinal stromal tumor decreased response Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT A829P demonstrated a decreased response to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT V560_Y578del gastrointestinal stromal tumor sensitive Imatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line harboring KIT V560_Y578del demonstrated sensitivity to Gleevec (imatinib) in culture (PMID: 25239608). 25239608
KIT V560_Y578del gastrointestinal stromal tumor sensitive Ponatinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_Y578del demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). 25239608
KIT V560_Y578del gastrointestinal stromal tumor sensitive BGJ398 + Imatinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Gleevec (imatinib mesylate) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT V560_Y578del in culture (PMID: 25673643). 25673643
KIT P551_W557delinsL gastrointestinal stromal tumor sensitive Ponatinib Clinical Study Actionable In a clinical study, a GIST patient harboring KIT P551_W557delinsL, resistant to Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib), demonstrated sensitivity to Iclusig (ponatinib) treatment, which resulted in tumor regression and stable disease (PMID: 25239608). 25239608
KIT M552_V559del Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT M552_V559del in culture (PMID: 20633291). 20633291
KIT P551_E554del Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT P551_E554del Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT P551_E554del Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Sutent (sunitinib) in culture (PMID: 25239608). 25239608
KIT P551_E554del Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Gleevec (imatinib) in culture (PMID: 25239608). 25239608
KIT M541L chronic leukemia sensitive Imatinib Phase I Actionable In Phase I trials, KIT M541L has been associated with response to Gleevec (imatinib) in chronic eosinophilic leukemia, NOS (PMID: 25015329) and mastocytosis (PMID: 18795925). 25015329 18795925
KIT V560del KIT over exp thymic carcinoma sensitive Imatinib Clinical Study Actionable In a clinical case report, a patient with metastatic thymic carcinoma harboring KIT V560del with KIT over expression initially demonstrated stable disease and reduction in metastatic lesions following treatment with Gleevec (imatinib), but progressed after 6 months (PMID: 15201427). 15201427
KIT over exp Advanced Solid Tumor sensitive Derazantinib Preclinical - Cell culture Actionable In a preclinical study, Derazantinib (ARQ 087) inhibited growth of transformed cells overexpressing Kit in culture (PMID: 27627808). 27627808
KIT over exp seminoma sensitive Imatinib Clinical Study Actionable In a clinical case report, Gleevec (imatinib) in conjunction with third-line chemotherapy resulted in a complete response in a patient with stage IV chemoresistant pure seminoma with KIT over expression (PMID: 18751412). 18751412
KIT D816H Advanced Solid Tumor predicted - sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816H were more sensitive to treatment with Flumatinib in culture compared to Gleevec (imatinib) (PMID: 24205792). 24205792
KIT D816H Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, KIT D816H demonstrated resistance to Stivarga (regorafenib) in an in vitro assay, and conferred secondary resistance to Stivarga (regorafenib) in transformed cells expressing other KIT mutations (PMID: 25239608). 25239608
KIT D816H Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT D816H demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT D816H Advanced Solid Tumor predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816H were more sensitive to treatment with Sutent (sunitinib) in culture compared to Gleevec (imatinib) (PMID: 24205792). 24205792
KIT W557_K558del KIT D816H Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT D816H Advanced Solid Tumor decreased response Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Gleevec (imatinib) in both culture and xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT D816H Advanced Solid Tumor decreased response Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT W557_K558del KIT D816H Advanced Solid Tumor decreased response Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). 25239608
KIT A829P KIT V559D Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were insensitive to Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT A829P KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT A829P melanoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P melanoma resistant Sunitinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Sutent (sunitinib) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT A829P demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT A829P melanoma resistant Imatinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P melanoma sensitive Nilotinib Preclinical Actionable In a preclinical study, Tasigna (nilotinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT W557_K558del KIT A829P Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Sutent (sunitinb) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT exon 11 KIT A829P gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 mutation and KIT A829P in culture (PMID: 27370604). 27370604
KIT D820Y KIT V559D Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture (PMID: 17699867). 17699867
KIT D820Y KIT V559D Advanced Solid Tumor sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture (PMID: 17699867). 17699867
KIT D820Y KIT V559D Advanced Solid Tumor sensitive Nilotinib Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture, with increased potency compared to Sprycel (dasatinib) or Nexavar (sorafenib) (PMID: 17699867). 17699867
KIT D820Y melanoma predicted - sensitive Sorafenib Clinical Study Actionable In a clinical case report, Nexavar (sorafenib) treatment resulted in stable disease in a patient with anal melanoma and pulmonary metastases harboring KIT D820Y (PMID: 20372153). 20372153
KIT D820Y melanoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). 29035277
KIT D820Y melanoma sensitive SEL201 Preclinical - Cell line xenograft Actionable In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cell lines harboring KIT D820Y in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). 29035277
KIT D820Y melanoma resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib mesylate) failed to inhibit MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). 29035277
KIT Y553S KIT V556_T574del KIT D820Y gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT D820Y was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring primary KIT V569_L576del and KIT Y553S mutations, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT exon 11 KIT exon 17 gastrointestinal stromal tumor predicted - sensitive PLX9486 Phase I Actionable In a Phase I trial, PLX9486 treatment resulted in partial response with 33% decrease of tumor size after 4 cycles of therapy in a patient with gastrointestinal stromal tumor harboring a primary KIT exon 11 mutation and a secondary KIT exon 17 mutation, who progressed on prior Gleevec (imatinib mesylate) and Sutent (sunitinib) therapies (CTOS Annual Meeting, Nov 2017, abstract # 2771952). detail...
KIT exon 17 gastrointestinal stromal tumor sensitive Avapritinib Phase I Actionable In a Phase I trial, BLU-285 demonstrated preliminary antitumor activity in gastrointestinal stromal tumor patients harboring KIT mutations, with reduced tumor burden in 38% (5/13) of patients, including 1 partial response and 4 stable diseases, and 3 of the 5 responding patients harbored KIT exon 17 mutations (EORTC-NCI-AACR 2016, Abs 6LBA). detail...
KIT exon 17 Advanced Solid Tumor sensitive Avapritinib Preclinical Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of various tumor cell lines harboring KIT exon 17 mutations in culture, and induced tumor regression in an allograft animal model (PMID: 29093181). 29093181
KIT exon 17 gastrointestinal stromal tumor predicted - sensitive PLX9486 Phase I Actionable In a Phase I trial, PLX9486 demonstrated safety and preliminary efficacy, resulted in a progression-free survival of more than 24 weeks and partial response in 8.3% (2/24) of patients with advanced solid tumors, 20 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT exon 17 gastrointestinal stromal tumor predicted - sensitive Pexidartinib + PLX9486 Phase I Actionable In a Phase I trial, PLX9486 and Pexidartinib (PLX3397) combination therapy demonstrated safety and preliminary efficacy, resulted in a partial response rate of 8.3% (1/12) and progression-free survival not yet reached in patients with advanced solid tumors, 11 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT T417_D419delinsI Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T417_D419delinsI were sensitive to treatment with Sutent (sunitinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT T417_D419delinsI Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T417_D419delinsI were sensitive to treatment with Flumatinib, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT T417_D419delinsI Advanced Solid Tumor conflicting Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation in transformed cells over expressing KIT T417_D419delinsI in culture (PMID: 16015387). 16015387
KIT T417_D419delinsI Advanced Solid Tumor conflicting Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T417_D419delinsI were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT exon 11 KIT V654A gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion mutation and KIT V654A in culture (PMID: 27370604). 27370604
KIT exon 11 melanoma predicted - sensitive Imatinib Clinical Study Actionable In a clinical case report, Gleevec (imatinib mesylate) treatment resulted in partial response in a patient with metastasized anal melanoma harboring a 21 base-pair duplication in exon 11 of KIT, reduced pulmonary metastasis by 60% (PMID: 20372153). 20372153
KIT exon 11 gastrointestinal stromal tumor sensitive Nilotinib Phase III Actionable In a Phase III trial, a 24 month progression free survival was observed in 69.6% of advanced GIST patients harboring KIT exon 11 mutations when treated with Tasigna (nilotinib) (J Clin Oncol May 2013 vol. 31 no. 15_suppl 10501). detail...
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive Pexidartinib + PLX9486 Phase I Actionable In a Phase I trial, PLX9486 and Pexidartinib (PLX3397) combination therapy demonstrated safety and preliminary efficacy, resulted in a partial response rate of 8.3% (1/12) and progression-free survival not yet reached in patients with advanced solid tumors, 11 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT exon 11 gastrointestinal stromal tumor sensitive Regorafenib Phase II Actionable In a Phase II clinical trial, treatment with Stivarga (regorafenib) resulted in a clinical benefit rate of 76% (25/33), a median progression-free survival (PFS) of 13.2 months, and a median overall survival of 25 months in patients with gastrointestinal stromal tumors, with patients with KIT exon 11 mutations demonstrating the longest PFS of 13.4 months (PMID: 27371698). 27371698
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive DCC-2618 Preclinical - Cell line xenograft Actionable In a preclinical study, DCC-2618 inhibited Kit phosphorylation and tumor growth in a gastrointestinal stromal tumor cell line xenograft model harboring a KIT exon 11 deletion mutation (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 increased growth inhibition and decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations in culture, and improved survival and inhibited tumor growth in a KIT exon 11-mutant GIST cell line xenograft model, with increased efficacy compared to either agent alone (PMID: 27370604). 27370604
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib Phase III Actionable In a Phase III trial, Gleevec (imatinib) treatment resulted in longer overall survival (OS) (66 vs 40 months) in gastrointestinal stromal tumor (GIST) patients harboring KIT exon 11 mutations compared to KIT and PDGFRA wild-type patients, while subtypes of KIT exon 11 mutations (deletion, insertation/duplication, point mutation) did not affect OS outcome (PMID: 28196207; NCT00009906). 28196207
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib Phase III Actionable In a Phase III trial, a long-term analysis of gastrointestinal stromal tumor (GIST) patients treated with Gleevec (imatinib) demonstrated patients harboring KIT exon 11 mutations had a median progression-free survival of 39.4 months, and median overall survival was not reached, with 69.1% of patients with KIT exon 11 mutations alive at 5 years (PMID: 26687836; NCT00367861). 26687836
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive Ponatinib Phase II Actionable In a Phase II trial, Iclusig (ponatinib) treatment resulted in partial response in 7% (2/27), stable disease in 59% (16/27), a median progression free survival of 4.3 months and a median overall survival of 15.0 months in gastrointestinal stromal tumor patients harboring KIT exon 11 mutations after prior tyrosine kinase inhibitor treatment failure (J Clin Oncol 33, 2015 (suppl; abstr 10535)). detail...
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive PLX9486 Phase I Actionable In a Phase I trial, PLX9486 demonstrated safety and preliminary efficacy, resulted in a progression-free survival of more than 24 weeks and partial response in 8.3% (2/24) of patients with advanced solid tumors, 20 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib + XAV939 Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of XAV939 and Gleevec (imatinib) resulted in decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations compared to Gleevec (imatinib) alone, in culture (PMID: 28611108). 28611108
KIT exon 11 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), which included a partial response of 38.5% (10/26) and a progression free survival of 5.4 months in melanoma patients harboring KIT exon 11 mutations (PMID: 28327988). 28327988
KIT exon 11 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 5% (1/19) and partial response in 21% (4/19) of melanoma patients harboring KIT exon 11 or exon 13 mutations (PMID: 28843487; NCT01168050). 28843487
KIT exon 11 gastrointestinal stromal tumor decreased response Sunitinib Clinical Study Actionable In a retrospective analysis, GIST patients with KIT exon 11 mutations showed decreased benefit compared to patients with exon 9 mutations, with median PFS of 7.0 months with exon 11 mutations vs. 12.3 months with exon 9 mutations, and an ORR of 6% (9/143) vs. 19% (8/42) following treatment with Sutent (sunitinib) (PMID: 26772734). 26772734
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib + PKF118-310 Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of PKF118-310 and Gleevec (imatinib) resulted in decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations compared to Gleevec (imatinib) alone, in culture (PMID: 28611108). 28611108
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive Dasatinib Phase II Actionable In a Phase II clinical trial, Sprycel (dasatinib) demonstrated preliminary activity in patients with Gleevec (imatinib)-resistant gastrointestinal stromal tumor (GIST), including patients harboring KIT exon 11 mutations, with a partial response rate of 32% (15/47), median progression-free survival of 2.0 months, and overall survival of 19 months (J Clin Oncol 29: 2011 (suppl; abstr 10006)). detail...
KIT K558delinsNP Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K558delinsNP demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K558delinsNP Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K558delinsNP demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K558delinsNP Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing K558delinsNP demonstrated sensitivity to treatment with Stivarga (regorafenib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K558delinsNP Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing K558delinsNP demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT N822K Advanced Solid Tumor predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Sutent (sunitinib) in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT N822K Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT N822K acute myeloid leukemia sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 29093181). 29093181
KIT N822K acute myeloid leukemia sensitive DCC-2618 Preclinical - Pdx Actionable In a preclinical study, DCC-2618 induced tumor regression in a patient-derived xenograft (PDX) model of acute myeloid leukemia harboring KIT N822K (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT N822K acute myeloid leukemia sensitive BPR1J373 Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KIT N822K demonstrated sensitivity to treatment with BPR1J373, showing inhibition of Kit phosphorylation and apoptotic induction in culture, and tumor regression in xenograft models (PMID: 27512117). 27512117
KIT N822K leukemia sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited Kit signaling and viability in leukemia cells harboring KIT N822K in culture (PMID: 21482694). 21482694
KIT N822K Advanced Solid Tumor predicted - sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Flumatinib in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT N822K gastrointestinal stromal tumor resistant Imatinib Clinical Study Actionable In a clinical case study, KIT N822K was identified in the tumor of a gastrointestinal stromal tumor patient that was resistant to Gleevec (imatinib mesylate) treatment. (PMID: 26316776). 26316776
KIT N822K KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT N822K and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation and inhibition of Kit, Erk 1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT N822K KIT V559D Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT N822K and KIT V559D were insensitive to Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT W557_K558del KIT N822K Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT N822K Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT N822K Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT N822K Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Sutent (sunitinb) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558delinsCE KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT N822K was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT W557_K558delinsCE, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT V569_L576del KIT V654A KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT V654A and KIT N822K were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V569_L576del, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT D816V KIT V560G mast-cell leukemia sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of a mast cell leukemia cell line harboring KIT D816V and V560G in culture (PMID: 29093181). 29093181
KIT D816V KIT V560G mast cell neoplasm resistant Quizartinib Preclinical Actionable In a preclinical study, KIT D816V conferred resistance to Quizartinib in a mast cell line harboring both KIT V560G and KIT D816V in culture (PMID: 23497317). 23497317
KIT D816V KIT V560G mast-cell leukemia sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis in a mast-cell leukemia cell line harboring both KIT V560G and KIT D816V in culture (PMID: 18024392). 18024392
KIT D816V KIT V560G mast-cell leukemia sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited growth of a human mast cell line harboring both KIT V560G and KIT D816V in culture (PMID: 24552773). 24552773
KIT D816V KIT V560G mast-cell leukemia sensitive BPR1J373 Preclinical - Cell culture Actionable In a preclinical study, a mast-cell leukemia cell line simultaneously harboring KIT D816V and KIT V560G was sensitive to BPR1J373 in culture, demonstrating inhibition of Kit phosphorylation and apoptotic activity (PMID: 27512117). 27512117
KIT V560G Advanced Solid Tumor sensitive Nilotinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560G demonstrated inhibition of cell proliferation and tumor regression both in culture and in vivo when treated with Tasigna (nilotinib) (PMID: 20442311). 20442311
KIT V560G mast-cell leukemia sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of mast cell leukemia cells harboring KIT V560G in culture (PMID: 29093181). 29093181
KIT V560G Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V560G demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557G Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing KIT W557G in culture (PMID: 23567324). 23567324
KIT V560del KIT V654A Advanced Solid Tumor sensitive Nilotinib Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V560del/V654A double mutation in culture (PMID: 17699867). 17699867
KIT V560del Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited growth of transformed cell lines over expressing KIT V560del in culture (PMID: 19861435). 19861435
KIT V560del Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, Sutent (sunitinib) inhibited growth of transformed cell lines over expressing KIT V560del in culture (PMID: 19861435). 19861435
KIT V559del gastrointestinal stromal tumor sensitive G007-LK + Imatinib Preclinical Actionable In a preclinical study, the combination of G007-LK and Gleevec (imatinib) demonstrated increased anti-tumor activity compared to either agent alone in a mouse model of gastrointestinal stromal tumor expressing Kit V558del (corresponding to human V559del) (PMID: 28611108). 28611108
KIT D816F Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816F were resistant to Gleevec (imatinib mesylate) in culture (PMID: 16397263). 16397263
KIT V560_L576del gastrointestinal stromal tumor sensitive Ponatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient derived GIST cell line harboring KIT V560_L576del demonstrated sensitivity to Iclusig (ponatinib) in both culture and PDX models, resulting in phosphorylation inhibition of Akt, Kit, and Erk (PMID: 25239608). 25239608
KIT V560_L576del gastrointestinal stromal tumor sensitive Imatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient derived GIST cell line harboring KIT V560_L576del demonstrated sensitivity to Gleevec (imatinib) in both culture and PDX models, resulting in phosphorylation inhibition of Akt, Kit, and Erk (PMID: 25239608). 25239608
KIT V560_L576del KIT V654A gastrointestinal stromal tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_L576del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT D816G ROS1 fusion non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion developed resistance to treatment with Xalkori (crizotinib) and was subsequently found to have acquired KIT D816G (PMID: 29636358). 29636358
KIT exon 11 del gastrointestinal stromal tumor predicted - sensitive Imatinib Phase III Actionable In a Phase III trial, gastrointestinal stromal tumor patients harboring KIT exon 11 deletions or indels demonstrated improved improved recurrence-free survival (RFS) with 3-year adjuvant Gleevec (imatinib) treatment (5-year RFS, 70%), compared to patients receiving 1-year treatment (5-year RFS, 41.3%) (PMID: 28334365). 28334365
KIT W557R melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT W557R demonstrating a partial response and progression free survival of 35.4 months and overall survival of 35.4 months (PMID: 28327988). 28327988
KIT D579del thymic carcinoma sensitive Imatinib Clinical Study Actionable In a clinical case report, a patient with thymic carcinoma harboring KIT D579del achieved disease stabilization following treatment with Gleevec (imatinib) (PMID: 24419427). 24419427
KIT I571_D579dup Advanced Solid Tumor predicted - resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT I571_D579dup Advanced Solid Tumor predicted - resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT I571_D579dup Advanced Solid Tumor predicted - resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT P577_D579del thymic carcinoma sensitive Sorafenib Clinical Study Actionable In a clinical case report, a patient with advanced thymic carcinoma harboring KIT P577_D579del demonstrated response to treatment with Nexavar (sorafenib), with a decrease in tumor size (PMID: 20970876). 20970876
KIT Y553N thymic carcinoma sensitive Imatinib Clinical Study Actionable In a clinical case report, a patient with metastatic thymic carcinoma harboring KIT Y553N demonstrated improved clinical performance and reduction in metastatic lesions following treatment with Gleevec (imatinib) (PMID: 21969494). 21969494
KIT act mut melanoma sensitive Imatinib Guideline Actionable Gleevec (imatinib) is included in guidelines as second-line therapy for melanoma patients with KIT activating mutations (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 not applicable N/A Guideline Diagnostic KIT activating mutations aid the diagnosis of gastrointestinal stromal tumor (NCCN.org). 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 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 V559D KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V559D and KIT V654A were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT V559D Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). 21689725
KIT V559D Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). 21689725
KIT V559D Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D were sensitive to Gleevec (imatinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT V559D Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D were sensitive to Sutent (sunitinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D were sensitive to Flumatinib, demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT V559D melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V559D demonstrating a partial response and progression free survival of 28.3 months and overall survival of 28.3 months (PMID: 28327988). 28327988
KIT V559D Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V559D demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT D816V mast cell neoplasm predicted - sensitive Avapritinib Phase I Actionable In a Phase I trial, patients with either aggressive systemic mastocytosis, mast cell leukemia, or systemic mastocytosis with an associated hematologic neoplasm harboring KIT D816V demonstrated a reduction in mast cell burden and a decrease in KIT D816V allelic fraction when treated with BLU-285 (ASH Annual Meeting, Dec 2017, Plenary 2). detail...
KIT D816V Indication other than cancer resistant Imatinib FDA approved Actionable Gleevec (imatinib) is not indicated for patients with aggressive systemic mastocytosis harboring KIT D816V (FDA.gov). detail...
KIT D816V Advanced Solid Tumor resistant Cabozantinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Cometriq (cabozantinib) in culture (PMID: 24205792). 24205792
KIT D816V Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Gleevec (imatinib mesylate) in culture (PMID: 15790786). 15790786
KIT D816V Advanced Solid Tumor resistant Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) did not inhibit growth of transformed cells expressing KIT D816V in culture (PMID: 22301675). 22301675
KIT D816V Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, KIT D816V mutations demonstrated resistance to Sutent (sunitinib) in a biochemical assay (PMID: 19164557). 19164557
KIT D816V Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT D816V Advanced Solid Tumor decreased response Nilotinib Preclinical Actionable In a preclinical study, Tasigna (nilotinib) decreased viability of cells expressing KIT D816V in culture, but did not inhibit KIT phosphorylation or growth of KIT D816V-expressing tumors in mouse models (PMID: 20442311). 20442311
KIT D816V Advanced Solid Tumor resistant Quizartinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Quizartinib in culture (PMID: 23497317). 23497317
KIT D816V hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101, as compared to Quizartinib, inhibited cell proliferation of transformed 32Dcl3 murine myeloid cells expressing human Kit D816V (PMID: 29187377). 29187377
KIT D816V Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Flumatinib in culture (PMID: 24205792). 24205792
KIT D816V Advanced Solid Tumor predicted - sensitive BPR1J373 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816V were sensitive to BPR1J373, demonstrating inhibition of Kit phosphorylation (PMID: 27512117). 27512117
KIT D816V hematologic cancer resistant Imatinib Preclinical Actionable In a preclinical study, a mouse myeloid cell line expressing KIT D816V demonstrated resistance to Gleevec (imatinib) in culture (PMID: 12481435). 12481435
KIT D816V acute myeloid leukemia sensitive Dasatinib + Cytarabine Clinical Study Actionable In a clinical case study, a patient with acute myeloid leukemia harboring KIT D816V achieved long-term remission and loss of KIT D816V following treatment with the combination of Sprycel (dasatinib) and Cytosar-U (cytarabine) (PMID: 18986703). 18986703
KIT D816V hematologic cancer resistant Sorafenib Preclinical Actionable In a preclinical study, transformed hematopoietic cells expressing KIT D816V demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 17229632). 17229632
KIT D816V NRAS Q61R melanoma no benefit Pembrolizumab + Trametinib Clinical Study Actionable In a clinical study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312). 28514312
KIT N505I melanoma sensitive Sorafenib Preclinical Actionable In a preclinical study, KIT N505I induced phosphorylation of KIT, ERK, and AKT, and was inhibited by Nexavar (sorafenib) in cell culture of melanocytes, demonstrating sensitivity of N505I to sorafenib (PMID: 24317392). 24317392
KIT N505I melanoma predicted - sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) decreased phosphorylation of KIT, AKT, and ERK in melanocytes expressing KIT N505I in culture (PMID: 24317392). 24317392
KIT H697Y Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, Sutent (sunitinib) inhibited growth of transformed cell lines overexpressing KIT H697Y in culture (PMID: 19861435). 19861435
KIT H697Y Advanced Solid Tumor decreased response Imatinib Preclinical Actionable In a preclinical study, transformed cell lines overexpressing KIT H697Y demonstrated reduced sensitivity to Gleevec (imatinib mesylate)-induced growth inhibition in culture (PMID: 19861435). 19861435
KIT V654A Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16751810). 16751810
KIT V654A Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated some sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT K558_V560del KIT V654A gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT V654A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT K558_V560del, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT V560D KIT V654A Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/V654A double mutation in culture (PMID: 20633291). 20633291
KIT V560D KIT V654A Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A were resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT W557_K558del KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and V654A (PMID: 29093181). 29093181
KIT W557_K558del KIT V654A Advanced Solid Tumor no benefit Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). 25239608
KIT exon 13 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), which included a partial response in 7.7% (1/13) of melanoma patients harboring KIT exon 13 mutations (PMID: 28327988). 28327988
KIT exon 13 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 5% (1/19) and partial response in 21% (4/19) of melanoma patients harboring KIT exon 11 or exon 13 mutations (PMID: 28843487; NCT01168050). 28843487
KIT exon 13 gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a gastrointestinal stromal tumor cell line harboring a KIT exon 13 mutation in culture (PMID: 27370604). 27370604
KIT K558_G565delinsR gastrointestinal stromal tumor sensitive Cabozantinib Preclinical - Pdx Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) resulted in tumor regression, decreased mitotic activity, and increased apoptotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT K558_G565delins (PMID: 27777285). 27777285
KIT K558_G565delinsR gastrointestinal stromal tumor sensitive Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib) treatment resulted in tumor regression and decreased mitotic activity in gastrointestinal stromal tumor patient derived xenograft (PDX) models harboring KIT K558_G565delinsR (PMID: 27777285). 27777285
KIT positive germ cell cancer resistant Imatinib Phase II Actionable In a small Phase II study, 18 patients with KIT-positive refractory germ cell tumors treated with Gleevec (imatinib) experienced no significant antitumor activity (PMID: 16462496). 16462496
KIT positive gastrointestinal stromal tumor sensitive Imatinib FDA approved Actionable In a Phase II trial that supported FDA approval, treatment with Gleevec (imatinib) resulted in an overall response rate of 38% (56/147) and a median duration of response of 13 weeks in patients with metastatic or unresectable KIT-positive GIST (PMID: 12374669). 12374669
KIT positive breast cancer predicted - sensitive Imatinib + Letrozole Phase 0 Actionable In a pilot trial, Gleevec (imatinib mesylate) and Femara (letrozole) combination treatment resulted in clinical partial response in 90% (9/10) and stable disease in 10% (1/10) of the evaluable patients with invasive hormone-sensitive breast cancer, 8 of the 13 enrolled patients had KIT-positive tumors (PMID: 18248884). 18248884
KIT positive prostate neuroendocrine neoplasm no benefit Imatinib Preclinical Actionable In a preclinical study, a prostate neuroendocrine tumor mouse model expressing Kit did not respond to Gleevec (imatinib), a result of impaired signaling of the Kit pathway (PMID: 27980106). 27980106
KIT V560D Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V560D Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V560D Advanced Solid Tumor sensitive Dasatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D were sensitive to Sprycel (dasatinib) in culture (PMID: 16397263). 16397263
KIT V560D Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V560D Advanced Solid Tumor sensitive Sorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D were sensitive to Nexavar (sorafenib) in culture (PMID: 22665524). 22665524
KIT V560D Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V560D melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V560D demonstrating a partial response and progression free survival of 8.6 months and overall survival of 23.5 months (PMID: 28327988). 28327988
KIT V560D Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT V560D in culture (PMID: 20633291). 20633291
KIT Y578C Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing KIT Y578C in culture (PMID: 23567324). 23567324
KIT P551_V555del gastrointestinal stromal tumor sensitive Sorafenib Preclinical - Pdx Actionable In a preclinical study, Nexavar (sorafenib) inhibited Erk signaling, induced apoptosis, resulted in tumor growth inhibition in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT P551_V555del (PMID: 19139124). 19139124
KIT D816Y Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT D816Y Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to Gleevec (imatinib mesylate) in culture (PMID: 16397263). 16397263
KIT D816Y Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Flumatinib in culture (PMID: 24205792). 24205792
KIT D816Y mast cell neoplasm sensitive Avapritinib Preclinical Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of murine mastocytoma cells harboring KIT D814Y (corresponding to human D816Y) in culture, and resulted in tumor regression in allograft animal models (PMID: 29093181). 29093181
KIT D816Y mast cell neoplasm sensitive DCC-2618 Preclinical - Cell culture Actionable In a preclinical study, DCC-2618 inhibited proliferation of a mouse mastocytosis cell line expressing KIT K816Y in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT D816Y Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT D820V gastrointestinal stromal tumor sensitive Avapritinib Phase I Actionable In a Phase I trial, BLU-285 treatment resulted in tumor reduction lasting through 15 cycles of treatment in a patient with gastrointestinal stromal tumor harboring KIT D820V, whose disease had progressed on previous Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib) treatment (PMID: 29093181; NCT02508532). 29093181
KIT N822I Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822I demonstrated resistance to Gleevec (imatinib) in culture (PMID: 21689725). 21689725
KIT N822I Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis of transformed cells expressing KIT N822I in culture (PMID: 21689725). 21689725
KIT S476I mast-cell leukemia predicted - sensitive Nilotinib Preclinical - Patient cell culture Actionable In a preclinical study, treatment with Tasigna (nilotinib) decreased proliferation of patient-derived neoplastic mast cells harboring KIT S476I in culture (PMID: 25209843). 25209843
KIT S476I mast-cell leukemia predicted - sensitive Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) decreased proliferation of patient-derived neoplastic mast cells harboring KIT S476I in culture (PMID: 25209843). 25209843
KIT S476I MET R988C gastrointestinal stromal tumor sensitive Bevacizumab + Sorafenib Clinical Study Actionable In a clinical case study, a GIST patient harboring KIT S476I and MET R988C demonstrated sensitivity to the combination treatment, Nexavar (sorafenib) and Avastin (bevacizumab), resulting in stable disease for 6 months (PMID: 25363205). 25363205
KIT W557_K558del Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT W557_K558del Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). 17699867
KIT W557_K558del Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and near complete tumor regression (PMID: 25239608). 25239608
KIT W557_K558del Advanced Solid Tumor sensitive Nilotinib Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) inhibited growth of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). 17699867
KIT W557_K558del gastrointestinal stromal tumor sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 treatment inhibited Erk phosphorylation and decreased expression of ETV1 and CXCR4 in gastrointestinal stromal tumor cells harboring KIT W557_K558del (PMID: 26936919). 26936919
KIT W557_K558del Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing W557_K558del demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT W557_K558del Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608