RET C618S
Gene Variant Detail

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Gene RET
Variant C618S
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions RET C618S lies within the extracellular domain of the Ret protein (UniProt.org). C618S is transforming in cell culture (PMID: 9230192), and therefore, is predicted to lead to a gain of Ret protein function.
Associated Drug Resistance
Category Variants Paths

RET mutant RET act mut RET C618S

RET mutant RET C618X RET C618S

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Transcript NM_020975.6
gDNA chr10:g.43113648T>A
cDNA c.1852T>A
Protein p.C618S
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020630.7 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_020975 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_001406765.1 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_020630 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_001406763.1 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43113648T>A c.1852T>A p.C618S RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C618S malignant pheochromocytoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in a partial response lasting 3.8 months in a patient with metastatic pheochromocytoma harboring RET C618S (PMID: 38661071; NCT03157128). 38661071
RET C618S 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 C618S; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). 32846061 detail... detail...