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Gene RET
Variant D631Y
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET D631Y lies within the extracellular domain of the Ret protein (UniProt.org). D631Y confers a gain of function on the Ret protein as demonstrated by induction of covalent Ret dimerization and phosphorylation (PMID: 10049754), increased Erk phosphorylation (PMID: 36166639), and transformation of cultured cells (PMID: 10049754, PMID: 36166639).
Associated Drug Resistance
Category Variants Paths

RET mutant RET act mut RET D631Y

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Transcript NM_020975.6
gDNA chr10:g.43114491G>T
cDNA c.1891G>T
Protein p.D631Y
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020975 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38
NM_020630 chr10:g.43114491G>T c.1891G>T p.D631Y RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET D631Y Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET D631Y in culture (PMID: 36166639). 36166639
RET D631Y Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET D631Y in culture (PMID: 36166639). 36166639