RET C618Y
Gene Variant Detail

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Gene RET
Variant C618Y
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET C618Y lies within the extracellular domain of the Ret protein (UniProt.org). C618Y results in increased phosphorylation of Akt and Erk1/2, promotes colony formation (PMID: 31364476), and is transforming in cell culture (PMID: 9230192).
Associated Drug Resistance
Category Variants Paths

RET mutant RET act mut RET C618Y

RET mutant RET C618X RET C618Y

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Transcript NM_020975.6
gDNA chr10:g.43113649G>A
cDNA c.1853G>A
Protein p.C618Y
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001406763.1 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_001406765.1 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_020975 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38
NM_020630 chr10:g.43113649G>A c.1853G>A p.C618Y RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C618Y 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 C618Y; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). 32846061 detail... detail...