Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Gene | IDH1 |
Variant | H315D |
Impact List | missense |
Protein Effect | no effect - predicted |
Gene Variant Descriptions | IDH1 H315D lies within an NADP-binding region of the Idh1 protein (UniProt.org). H315D confers resistance to an IDH1 inhibitor in the presence of IDH1 R132H, but does not lead to increased production of the oncometabolite 2HG (R(-)-2-hydroxyglutarate), and results in cytokine-independent growth and erythroid differentiation similar to wild-type protein in cell culture (PMID: 36222845), and therefore, is predicted to have no effect on Idh1 protein function. |
Associated Drug Resistance | Y |
Category Variants Paths |
IDH1 mutant IDH1 H315D |
Transcript | NM_005896.4 |
gDNA | chr2:g.208239911G>C |
cDNA | c.943C>G |
Protein | p.H315D |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001282386.1 | chr2:g.208239911G>C | c.943C>G | p.H315D | RefSeq | GRCh38/hg38 |
NM_005896.3 | chr2:g.208239911G>C | c.943C>G | p.H315D | RefSeq | GRCh38/hg38 |
NM_001282386.1 | chr2:g.208239911G>C | c.943C>G | p.H315D | RefSeq | GRCh38/hg38 |
NM_005896.4 | chr2:g.208239911G>C | c.943C>G | p.H315D | RefSeq | GRCh38/hg38 |
NM_001282387.1 | chr2:g.208239911G>C | c.943C>G | p.H315D | RefSeq | GRCh38/hg38 |
NM_001282387.1 | chr2:g.208239911G>C | c.943C>G | p.H315D | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
IDH1 R132C IDH1 D279N IDH1 H315D | acute myeloid leukemia | predicted - resistant | Ivosidenib | Case Reports/Case Series | Actionable | In a Phase I trial, IDH1 H315D and D279N were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). | 32380538 |
IDH1 R132H IDH1 H315D | leukemia | resistant | Ivosidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Tibsovo (ivosidenib) did not inhibit Idh1 activity and R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845). | 36222845 |
IDH1 R132H IDH1 H315D | leukemia | predicted - resistant | Vorasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Vorasidenib (AG-881) did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture (PMID: 36222845). | 36222845 |
IDH1 R132H IDH1 H315D | leukemia | predicted - resistant | IDH305 | Preclinical - Biochemical | Actionable | In a preclinical study, IDH305 did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture (PMID: 36222845). | 36222845 |
IDH1 R132H IDH1 H315D | leukemia | predicted - resistant | BAY1436032 | Preclinical - Biochemical | Actionable | In a preclinical study, BAY1436032 did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture (PMID: 36222845). | 36222845 |