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Ref Type

Journal Article

PMID

(37253112)

Authors

Hu C, Belur Nagaraj A, Shimelis H, Montalban G, Lee KY, Huang H, Lumby CA, Na J, Susswein LR, Roberts ME, Marshall ML, Hiraki S, LaDuca H, Chao E, Yussuf A, Pesaran T, Neuhausen SL, Haiman CA, Kraft P, Lindström S, Palmer JR, Teras LR, Vachon CM, Yao S, Ong I, Nathanson KL, Weitzel JN, Boddicker N, Gnanaolivu R, Polley EC, Mer G, Cui G, Karam R, Richardson ME, Domchek SM, Yadav S, Hruska KS, Dolinsky J, Weroha SJ, Hart SN, Simard J, Masson JY, Pang YP, Couch FJ

Title

Functional and clinical characterization of variants of uncertain significance identifies a hotspot for inactivating missense variants in RAD51C.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer research			2023 May 30		Cancer Res

URL

Abstract Text

Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk of breast and ovarian cancer. A large number of RAD51C missense variants of uncertain significance (VUS) have been identified, but the effects of the majority of these variants on RAD51C function and cancer predisposition have not been established. Here, analysis of 173 missense variants by a homology-directed repair (HDR) assay in reconstituted RAD51C-/- cells identified 30 non-functional (deleterious) variants, including 18 in a hotspot within the ATP binding region. The deleterious variants conferred sensitivity to cisplatin and olaparib and disrupted formation of RAD51C/XRCC3 and RAD51B/RAD51C/RAD51D/XRCC2 complexes. Computational analysis indicated the deleterious variant effects were consistent with structural effects on ATP-binding to RAD51C. A subset of the variants displayed similar effects on RAD51C activity in reconstituted human RAD51C depleted cancer cells. Case-control association studies of deleterious variants in women with breast and ovarian cancer and non-cancer controls showed associations with moderate breast cancer risk (odds ratio (OR)=3.92; 95%CI:2.18-7.59) and high ovarian cancer risk (OR=14.8; 95%CI:7.71-30.36), similar to protein-truncating variants. This functional data supports the clinical classification of inactivating RAD51C missense variants as pathogenic or likely pathogenic, which may improve the clinical management of variant carriers.

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Showing 1 to 27 of 27 entries

Gene	Variant	Impact	Protein Effect	Variant Description
RAD51C	P21S	missense	no effect - predicted	RAD51C P21S lies within a region of the Rad51c protein required for Holliday junction resolution activity (UniProt.org). P21S binds to Rad51b, Rad51d, and Xrcc3 to similar levels as wild-type protein in a yeast assay (PMID: 36099300) and retains the ability to induce foci formation in culture (PMID: 37253112), and therefore, is predicted to have no effect on Rad51c protein function.
RAD51C	T102I	missense	loss of function	RAD51C T102I lies within the region required for Holliday junction resolution activity and the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). T102I results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	D108G	missense	loss of function	RAD51C D108G lies within the region required for Holliday junction resolution activity and the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). D108G results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased Rad51 foci formation, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	G114R	missense	loss of function	RAD51C G114R lies within the region required for Holliday junction resolution activity and the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). G114R results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	G114V	missense	loss of function	RAD51C G114V lies within the region required for Holliday junction resolution activity and the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). G114V results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	G130R	missense	loss of function	RAD51C G130R lies within the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). G130R results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased colony formation, reduced Rad51 foci formation, and decreased homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	K131I	missense	loss of function	RAD51C K131I lies within the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). K131I results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased colony formation, reduced Rad51 foci formation, and decreased homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	T132I	missense	loss of function	RAD51C T132I does not lie within any known functional domains of the Rad51c protein (UniProt.org). T132I results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	T132R	missense	loss of function	RAD51C T132R lies within the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). T132R results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased colony formation, reduced Rad51 foci formation, and decreased homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	Q133E	missense	loss of function - predicted	RAD51C Q133E lies within the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). Q133E binds to Rad51d and supports cell proliferation to similar levels as wild-type Rad51c, but results in loss of interaction with Xrcc3, partial loss of interaction with Xrcc2, and reduced homology-directed DNA repair activity in culture (PMID: 37253112), and therefore, is predicted to lead to a loss of Rad51c protein function.
RAD51C	V140E	missense	loss of function	RAD51C V140E does not lie within any known functional domains of the Rad51c protein (UniProt.org). V140E results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased Rad51 foci formation, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	G150E	missense	loss of function	RAD51C G150E does not lie within any known functional domains of the Rad51c protein (UniProt.org). G150E results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	A155E	missense	loss of function	RAD51C A155E does not lie within any known functional domains of the Rad51c protein (UniProt.org). A155E results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased Rad51 foci formation, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	V156D	missense	loss of function	RAD51C V156D does not lie within any known functional domains of the Rad51c protein (UniProt.org). V156D results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	D159A	missense	loss of function	RAD51C D159A does not lie within any known functional domains of the Rad51c protein (UniProt.org). D159A results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	D159N	missense	unknown	RAD51C D159N does not lie within any known functional domains of the Rad51c protein (UniProt.org). D159N demonstrates partial rescue of mitomycin C hypersensitivity in chicken cells and Rad51 foci formation similar to wild-type Rad51c in human cells in culture (PMID: 20400964), but in another study results in decreased binding to Brca2, Palb2, Rad51 (PMID: 24141787), and Rad51d and demonstrates loss of interaction with Xrcc3 in cell culture (PMID: 37253112), and binds to Rad51b and Rad51c at reduced levels but to Xrcc3 similar to wild-type protein in a yeast assay (PMID: 36099300), and therefore, its effect on Rad51c protein function is unknown.
RAD51C	D159Y	missense	loss of function	RAD51C D159Y does not lie within any known functional domains of the Rad51c protein (UniProt.org). D159Y results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased Rad51 foci formation, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	S163R	missense	loss of function	RAD51C S163R does not lie within any known functional domains of the Rad51c protein (UniProt.org). S163R binds to Rad51d to similar levels of wild-type Rad51c, but results in loss of interaction with Xrcc3, partial loss of interaction with Xrcc2, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	R168G	missense	loss of function	RAD51C R168G lies within the Rad51b, Rad51d, and Xrcc3-interacting region of the Rad51c protein (UniProt.org). R168G results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, decreased colony formation, reduced Rad51 foci formation, and decreased homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	R214C	missense	unknown	RAD51C R214C does not lie within any known functional domains of the Rad51c protein (UniProt.org). R214C results in decreased interaction with Xrcc3 and Rad51b in a yeast-two-hybrid assay in one study (PMID: 21980511), but in another study binds to Rad51b, Rad51d, and Xrcc3 to similar levels of wild-type protein in a yeast assay (PMID: 36099300) and demonstrates homology-directed repair activity in cultured cells (PMID: 37253112), and therefore, its effect on Rad51c protein function is unknown.
RAD51C	R237P	missense	loss of function	RAD51C R237P does not lie within any known functional domains of the Rad51c protein (UniProt.org). R237P results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	D242N	missense	loss of function	RAD51C D242N does not lie within any known functional domains of the Rad51c protein (UniProt.org). D242N results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	A279P	missense	loss of function	RAD51C A279P does not lie within any known functional domains of the Rad51c protein (UniProt.org). A279P results in loss of interaction with Xrcc2, Xrcc3, and Rad51d, and reduced homology-directed DNA repair activity compared to wild-type Rad51c in culture (PMID: 37253112).
RAD51C	G302V	missense	loss of function - predicted	RAD51C G302V does not lie within any known functional domains of the Rad51c protein (UniProt.org). G302V binds to Rad51d and Xrcc2 and supports cell proliferation to similar levels as wild-type Rad51c, but results in loss of interaction with Xrcc3, altered Rad51 foci formation, and reduced homology-directed DNA repair activity in culture (PMID: 37253112), and therefore, is predicted to lead to a loss of Rad51c protein function.
RAD51C	G306R	missense	unknown	RAD51C G306R does not lie within any known functional domains of the Rad51c protein (UniProt.org). G306R results in altered homology-directed DNA repair activity and Rad51 foci formation in culture (PMID: 37253112), but has not been fully biochemically characterized and therefore, its effect on Rad51c protein function is unknown.
RAD51C	D348V	missense	loss of function - predicted	RAD51C D348V does not lie within any known functional domains of the Rad51c protein (UniProt.org). D348V results in reduced homology-directed DNA repair activity in culture (PMID: 37253112), and therefore, is predicted to lead to a loss of Rad51c protein function.
RAD51C	R366Q	missense	loss of function - predicted	RAD51C R366Q does not lie within any known functional domains of the Rad51c protein (UniProt.org). R366Q results in Chk2 activation and Rad51 foci formation similar to wild-type (PMID: 20400964), and complements sensitivity to DNA damage and homologous recombination repair activity in RAD51C-null cells in culture (PMID: 37253112), and similar interaction with Rad51b, Rad51d, and Xrcc3 to wild-type Rad51c in yeast assays (PMID: 36099300), but moderately increased chromosomal aberrations, reduced G2/M accumulation and DNA synthesis in cultured cells, and decreased homologous recombination activity in a reporter assay (PMID: 22167183) and in culture (PMID: 25292178), and therefore, is predicted to lead to a loss of Rad51c protein function.

Showing 1 to 27 of 27 entries

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Showing 1 to 63 of 63 entries

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
RAD51C A155E	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C A155E sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C A155E	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C A155E sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C A279P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C A279P sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C A279P	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C A279P sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C C135Y	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C C135Y sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D108G	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D108G sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D108G	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D108G sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D159A	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D159A sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D159A	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D159A sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D159Y	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D159Y sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D159Y	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D159Y sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D242N	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D242N sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D242N	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D242N sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D348V	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D348V sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C D348V	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C D348V sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G114R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G114R sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G114V	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G114V sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G114V	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G114V sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G125V	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G125V sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G125V	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G125V sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G130R	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G130R sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G130R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G130R sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G130R	osteosarcoma	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G130R sensitized RAD51C-null osteosarcoma cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell survival (PMID: 37253112).	37253112
RAD51C G150E	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G150E sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G150E	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G150E sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G153D	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G153D sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G153D	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G153D sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G162E	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G162E sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G162E	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G162E sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G302V	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G302V sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G302V	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G302V sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C G306R	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C G306R sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C K131I	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C K131I sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C K131I	osteosarcoma	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C K131I sensitized RAD51C-null osteosarcoma cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell survival (PMID: 37253112).	37253112
RAD51C K131I	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C K131I sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C L138F	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C L138F sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C L138F	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C L138F sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C L27P	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C L27P sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C L27P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C L27P sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C Q133E	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C Q133E sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C Q133E	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C Q133E sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C R168G	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C R168G sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C R168G	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C R168G sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C R168G	osteosarcoma	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C R168G sensitized RAD51C-null osteosarcoma cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell survival (PMID: 37253112).	37253112
RAD51C R237P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C R237P sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C R237P	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C R237P sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C R312W	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C R312W sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C R312W	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C R312W sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C S163R	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C S163R sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C S163R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C S163R sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T102I	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T102I sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T102I	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T102I sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T132I	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T132I sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T132I	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T132I sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T132R	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T132R sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T132R	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T132R sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T132R	osteosarcoma	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T132R sensitized RAD51C-null osteosarcoma cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell survival (PMID: 37253112).	37253112
RAD51C T336P	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T336P sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C T336P	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C T336P sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C V140E	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C V140E sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C V140E	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C V140E sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C V156D	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C V156D sensitized RAD51C-deficient cells to Lynparza (olaparib) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112
RAD51C V156D	Advanced Solid Tumor	sensitive	Cisplatin	Preclinical - Cell culture	Actionable	In a preclinical study, the expression of RAD51C V156D sensitized RAD51C-deficient cells to Platinol (cisplatin) treatment in culture, resulting in decreased cell proliferation (PMID: 37253112).	37253112

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