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| Gene | RET |
| Variant | C634L |
| Impact List | missense |
| Protein Effect | gain of function |
| Gene Variant Descriptions | RET C634L lies within the cysteine-rich region of the Ret protein (PMID: 9879991). C634L results in ligand-independent dimerization of Ret and increased cell proliferation in culture (PMID: 27841748). |
| Associated Drug Resistance | |
| Category Variants Paths |
RET mutant RET act mut RET C634L RET mutant RET C634X RET C634L |
| Transcript | NM_020975.6 |
| gDNA | chr10:g.43114500_43114501delTGinsCT |
| cDNA | c.1900_1901delTGinsCT |
| Protein | p.C634L |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_020975 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_001406744.1 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_020630 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_001406759.1 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_020630.7 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_001406743.1 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_020975.5 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_020630.5 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_001406760.1 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_001406783.1 | chr10:g.43123795_43123796delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_001406786.1 | chr10:g.43123795_43123796delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| NM_020975.6 | chr10:g.43114500_43114501delTGinsCT | c.1900_1901delTGinsCT | p.C634L | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| RET C634L | 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 C634L; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). | detail... detail... 32846061 |