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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 |
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 |
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 |