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Molecular Profile	Treatment Approach
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Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
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Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
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Gene	Variant	Impact	Protein Effect	Variant Description
RET	G533C	missense	gain of function	RET G533C lies within the extracellular domain of the Ret protein (UniProt.org). G553C results in increased Erk phosphorylation (PMID: 36166639) and Ret autophosphorylation, enhanced cell proliferation, micronuclei formation, and colony formation, decreased apoptosis and expression of thyroid-specific genes in culture (PMID: 21834681), transformation in culture (PMID: 36166639), and increased liver metastasis in mouse models (PMID: 21834681).
RET	D567N	missense	gain of function	RET D567N lies within the extracellular domain of the Ret protein (UniProt.org). D567N results in increased phosphorylation of Ret and Erk, IL3-independent growth in culture, and tumor formation in a mouse model (PMID: 36166639).
RET	D567Y	missense	gain of function	RET D567Y lies within the extracellular domain of the Ret protein (UniProt.org). D567Y results in increased phosphorylation of Ret and Erk, IL3-independent growth in culture, and tumor formation in a mouse model (PMID: 36166639).
RET	D571N	missense	gain of function	RET D571N lies within the extracellular domain of the Ret protein (UniProt.org). D571N confers a gain of function to Ret as demonstrated by increased Erk phosphorylation and IL3-independent growth in culture (PMID: 36166639).
RET	E574D	missense	gain of function	RET E574D lies within the extracellular domain of the Ret protein (UniProt.org). E574D confers a gain of function to Ret as demonstrated by increased Erk phosphorylation and IL3-independent growth in culture (PMID: 36166639).
RET	D584N	missense	gain of function	RET D584N lies within the extracellular domain of the Ret protein (UniProt.org). D584N confers a gain of function to Ret as demonstrated by increased Erk phosphorylation and IL3-independent growth in culture (PMID: 36166639).
RET	Y606C	missense	gain of function	RET Y606C lies within the extracellular domain of the Ret protein (UniProt.org). Y606C results in ligand independent dimerization and constitutive phosphorylation of Ret, increased Erk2 phosphorylation (PMID: 18248647, PMID: 36166639), and transformation in culture (PMID: 36166639).
RET	G607C	missense	gain of function	RET G607C lies within the extracellular domain of the Ret protein (UniProt.org). G607C confers a gain of function to Ret as demonstrated by increased Erk phosphorylation and IL3-independent growth in culture (PMID: 36166639).
RET	C620R	missense	gain of function	RET C620R lies within the extracellular domain of the Ret protein (PMID: 9230192). C620R results in decreased cell surface Ret expression, but also results in increased Ret and Shc phosphorylation, activation of transcription in a reporter assay, transformation in cell culture (PMID: 9879991, PMID: 9230192), increased Erk phosphorylation and IL3-independent growth in culture (PMID: 36166639).
RET	D631Y	missense	gain of function	RET D631Y lies within the extracellular domain of the Ret protein (UniProt.org). D631Y confers a gain of function on the Ret protein as demonstrated by induction of covalent Ret dimerization and phosphorylation (PMID: 10049754), increased Erk phosphorylation (PMID: 36166639), and transformation of cultured cells (PMID: 10049754, PMID: 36166639).

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
RET C634R	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling and viability in transformed cells expressing RET C634R in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639).	36166639
RET C634R	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and viability in transformed cells expressing RET C634R in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639).	36166639
RET D567N	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling and viability in transformed cells expressing RET D567N in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639).	36166639
RET D567N	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and viability in transformed cells expressing RET D567N in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639).	36166639
RET D567Y	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and viability in transformed cells expressing RET D567Y in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639).	36166639
RET D567Y	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling and viability in transformed cells expressing RET D567Y in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639).	36166639
RET C620R	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell culture	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET C620R in culture (PMID: 36166639).	36166639
RET C620R	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET C620R in culture (PMID: 36166639).	36166639
RET D631_L633delinsE	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET D631_L633delinsE in culture (PMID: 36166639).	36166639
RET D631_L633delinsE	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell culture	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET D631_L633delinsE in culture (PMID: 36166639).	36166639
RET D631Y	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET D631Y in culture (PMID: 36166639).	36166639
RET D631Y	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell culture	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET D631Y in culture (PMID: 36166639).	36166639
RET E632_L633del	Advanced Solid Tumor	conflicting	Pralsetinib	Preclinical - Cell culture	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET E632_L633del in culture (PMID: 36166639).	36166639
RET E632_L633del	Advanced Solid Tumor	conflicting	Selpercatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET E632_L633del in culture (PMID: 36166639).	36166639
RET G607C	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET G607C in culture (PMID: 36166639).	36166639
RET G607C	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell culture	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET G607C in culture (PMID: 36166639).	36166639
RET M918T	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Cell culture	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET M918T in culture (PMID: 36166639).	36166639
RET M918T	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET M918T in culture (PMID: 36166639).	36166639
RET D571N	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Biochemical	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling in transformed cells expressing RET D571N in culture (PMID: 36166639).	36166639
RET D571N	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Biochemical	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling in transformed cells expressing RET D571N in culture (PMID: 36166639).	36166639
RET D584N	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Biochemical	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling in transformed cells expressing RET D584N in culture (PMID: 36166639).	36166639
RET D584N	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Biochemical	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling in transformed cells expressing RET D584N in culture (PMID: 36166639).	36166639
RET E574D	Advanced Solid Tumor	sensitive	Selpercatinib	Preclinical - Biochemical	Actionable	In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling in transformed cells expressing RET E574D in culture (PMID: 36166639).	36166639
RET E574D	Advanced Solid Tumor	sensitive	Pralsetinib	Preclinical - Biochemical	Actionable	In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling in transformed cells expressing RET E574D in culture (PMID: 36166639).	36166639

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