RET C620R
Gene Variant Detail

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Gene RET
Variant C620R
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance
Category Variants Paths

RET mutant RET act mut RET C620R

RET mutant RET C620X RET C620R

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Transcript NM_020975.6
gDNA chr10:g.43113654T>C
cDNA c.1858T>C
Protein p.C620R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020975 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_001406763.1 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_001406765.1 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_020630 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43113654T>C c.1858T>C p.C620R RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C620R medullary thyroid carcinoma predicted - sensitive Everolimus Case Reports/Case Series Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease of 116 weeks in a MEN2A patient with medullary thyroid cancer harboring a RET C620R mutation (PMID: 26294908; NCT01118065). 26294908
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 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 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 C620R; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). detail... detail... 32846061