RET A883F
Gene Variant Detail

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Gene RET
Variant A883F
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET A883F lies within the protein kinase domain of the Ret protein (UniProt.org). A883F confers a gain of function to the Ret protein as demonstrated by increased Ret kinase activity (PMID: 24561444) and is transforming in cell culture (PMID: 10445857, PMID: 10679286).
Associated Drug Resistance
Category Variants Paths

RET mutant RET A883X RET A883F

RET mutant RET act mut RET A883F

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Transcript NM_020975.6
gDNA chr10:g.43120120_43120121delGCinsTT
cDNA c.2647_2648delGCinsTT
Protein p.A883F
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001406744.1 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_020975 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_020630 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43120120_43120121delGCinsTT c.2647_2648delGCinsTT p.A883F RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET A883F Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited phosphorylation of Ret in transformed human cells expressing RET A883F in culture (PMID: 23526464). 23526464
RET A883F Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET A883F in culture (PMID: 15184865). 15184865
RET A883F medullary thyroid carcinoma sensitive Selpercatinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55, 5 complete and 33 partial responses) in previously treated adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations as detected by an approved test, including RET A883F; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). detail... detail... 32846061