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| Gene | RET |
| Variant | C618G |
| Impact List | missense |
| Protein Effect | gain of function - predicted |
| Gene Variant Descriptions | RET C618G lies within the extracellular domain of the Ret protein (UniProt.org). C618G 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 C618G RET mutant RET C618X RET C618G |
| Transcript | NM_020975.6 |
| gDNA | chr10:g.43113648T>G |
| cDNA | c.1852T>G |
| Protein | p.C618G |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_001406759.1 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_020975.6 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_001406763.1 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_001406765.1 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_020630.7 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_001406744.1 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_001406743.1 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_020975.5 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_001406760.1 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_020630 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_020975 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| NM_020630.5 | chr10:g.43113648T>G | c.1852T>G | p.C618G | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| RET C618G | 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 C618G; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). | 32846061 detail... detail... |