Gene Variant Detail

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Gene RET
Variant Y806C
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions RET Y806C lies within the protein kinase domain of the Ret protein (UniProt.org). Y806C is predicted to lead to a gain of Ret protein function as indicated by transformation of cultured cells in one study (PMID: 10679286), and has also been demonstrated to occur as a secondary resistance mutation in conjunction with other RET mutations (PMID: 19029224).
Associated Drug Resistance Y

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Transcript NM_020975.5
gDNA chr10:g.43119555A>G
cDNA c.2417A>G
Protein p.Y806C
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020630.5 chr10:g.43119555A>G c.2417A>G p.Y806C RefSeq GRCh38/hg38
NM_020975 chr10:g.43119555A>G c.2417A>G p.Y806C RefSeq GRCh38/hg38
NM_020630 chr10:g.43119555A>G c.2417A>G p.Y806C RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43119555A>G c.2417A>G p.Y806C RefSeq GRCh38/hg38

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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET Y806C Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited phosphorylation of Ret in transformed human cells expressing RET Y806C in culture (PMID: 23526464). 23526464
RET C634R RET Y806C Advanced Solid Tumor resistant Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET Y806C were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). 19029224
RET V804M RET Y806C thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Compound germline RET V840M and Y806C mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET act mut lung non-small cell carcinoma sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET phosphorylation and reduced viability of non-small cell lung cancer cells with RET activating mutations (Cancer Res April 15, 2013 73; 2084). detail...
RET mutant colorectal cancer sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235
RET mutant thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (60 vs 20 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET mutations (PMID: 27525386). 27525386
RET mutant pheochromocytoma predicted - sensitive Sunitinib Case Reports/Case Series Actionable In a Phase II trial (SNIPP), a patient with pheochromocytoma harboring a RET mutation achieved a partial response to treatment with Sutent (sunitinib), and demonstrated a 64% reduction in tumor volume and has remained on treatment for over 7 years (PMID: 31105270). 31105270
RET mutant Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of cancer cell lines harboring RET mutations in cultured and in cell line xenograft models (PMID: 23526464). 23526464
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib FDA approved 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), with five complete and 33 partial responses, in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations who were previously treated, while patients who had not been previously treated demonstrated an ORR of 73% (64/88), with ten complete and 54 partial responses (PMID: 32846061; NCT03157128). detail... 32846061
RET mutant thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908). 26294908
RET mutant cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited wild-type RET and RET mutations to prevent cell proliferation in cell culture (PMID: 17664273). 17664273
Molecular Profile Protein Effect Treatment Approaches
RET Y806C gain of function - predicted
RET C634R RET Y806C
RET V804M RET Y806C