RET C618R
Gene Variant Detail

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Gene RET
Variant C618R
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET C618R lies within the cysteine-rich region of the Ret protein (PMID: 9879991). C618R results in constitutive Ret phosphorylation and increased Ret kinase activity, but decreased Ret cell surface expression, and is transforming in cell culture (PMID: 9230192, PMID: 9879991).
Associated Drug Resistance
Category Variants Paths

RET mutant RET act mut RET C618R

RET mutant RET C618X RET C618R

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Transcript NM_020975.6
gDNA chr10:g.43113648T>C
cDNA c.1852T>C
Protein p.C618R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020630 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_001406765.1 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_001406763.1 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38
NM_020975 chr10:g.43113648T>C c.1852T>C p.C618R RefSeq GRCh38/hg38

Filtering

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C618R medullary thyroid carcinoma predicted - sensitive Sorafenib Case Reports/Case Series Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C618R (PMID: 20368568; NCT00390325). 20368568
RET C618R 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 C618R; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). 32846061 detail... detail...