[Paper-level Aggregated] PMCID: PMC6478919

Evidence Type(s): Functional

Summary: Mutation: T > C | Summary: The T > C variant at location 21 of BCL2 alters its RNA secondary structure and is associated with significant increases in BCL2 expression levels and mRNA stability, indicating a change in molecular function. It also correlates with increased BCL2 transcript levels and may affect spatial expression patterns.

Evidence Type: Functional Mutation: C > T | Summary: The C > T change at location 21 in BCL2 alters molecular function by stabilizing the BCL2 RNA secondary structure in vitro and correlates with increased BCL2 transcript levels.

Evidence Type: Functional Mutation: + 21 T > C | Summary: The + 21 T > C variant is evaluated for its structural consequences and is hypothesized to lead to a more stable transcript, resulting in increased BCL2 protein levels, indicating a change in molecular function.

Evidence Type: Functional Mutation: + 23 C > T | Summary: The + 23 C > T variant shows an insignificant change in structure and does not significantly alter molecular function, although it was included in studies evaluating BCL2 expression.

Evidence Type: Functional Mutation: 21 T > C | Summary: The 21 T > C variant in BCL2 is associated with a significant increase in BCL2 mRNA levels and leads to a more stable transcript, indicating an alteration in molecular function.

Gene→Variant (gene-first): BCL2(596):T > C BCL2(596):C > T BCL2(596):+ 21 T > C POTEF(728378):+ 23 C > T BCL2(596):21 T > C

Genes: BCL2(596) POTEF(728378)

Variants: T > C C > T + 21 T > C + 23 C > T 21 T > C

[Paper-level Aggregated] PMCID: PMC6478919

Evidence Type(s): Oncogenic

Summary: Mutation: + 21 T > C | Summary: The transition from C to T at location 21 of BCL2 contributes to tumor development or progression by leading to increased BCL2 protein levels, which are associated with resistance to paclitaxel treatment in ovarian cancer patients.

Gene→Variant (gene-first): BCL2(596):+ 21 T > C

Genes: BCL2(596)

Variants: + 21 T > C

[Paper-level Aggregated] PMCID: PMC6478919

Evidence Type(s): Predictive

Summary: Mutation: T > C variation at position 21 | Summary: The T > C variation at position 21 of the BCL2 sequence is associated with predicting response to the chemotherapy drug paclitaxel, correlating with both resistance and increased sensitivity to the drug. The presence of this variant is linked to increased BCL2 expression and transcript abundance when treated with paclitaxel, indicating its predictive value for therapy response.

Evidence Type: Predictive Mutation: rs1801018 | Summary: The variant rs1801018 is associated with resistance to paclitaxel and response to different treatments in ovarian cancer cell lines, indicating its potential predictive value for therapy sensitivity.

Gene→Variant (gene-first): BCL2(596):T > C variation at position 21 BCL2(596):rs1801018

Genes: BCL2(596)

Variants: T > C variation at position 21 rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 28

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs1801018 | Summary: The rs1801018 variant is associated with response to different treatments in ovarian cancer cell lines, indicating its potential predictive value for therapy sensitivity.

Gene→Variant (gene-first): 596:(AUC) of 39 596:rs1801018

Genes: 596

Variants: (AUC) of 39 rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 26

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: 21 T > C | Summary: The 21 T > C mutation in BCL2 was studied for its impact on spatial expression patterns, indicating that it alters molecular localization, although it did not show differences in localization compared to the reference form.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 25

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: 21 T > C | Summary: The 21 T > C variant is associated with increased BCL2 expression and correlates with resistance to paclitaxel treatment, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: 21 T > C | Summary: The 21 T > C variant contributes to tumor development by leading to higher BCL2 expression, which is linked to resistance against paclitaxel, a common chemotherapeutic agent.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: 21 T > C | Summary: The presence of the 21 T > C variant correlates with increased abundance of transcripts when treated with paclitaxel, suggesting a potential relationship with treatment response.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 22

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: 21 T > C | Summary: The variant 21 T > C in the BCL2 sequence correlates with increased sensitivity to paclitaxel, suggesting a potential predictive role in therapy response. Evidence Type: Functional | Mutation: 21 T > C | Summary: The 21 T > C variant leads to a more stable BCL2 transcript, which may result in higher protein levels, indicating an alteration in molecular function.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: 21 T > C | Summary: The 21 T > C variant in BCL2 is associated with a significant increase in BCL2 mRNA levels, indicating that this mutation alters the transcriptional activity of the gene. Evidence Type: Functional | Mutation: C instead of a T | Summary: The presence of a C instead of a T at position 21 in BCL2 correlates with an increase in BCL2 transcript levels, suggesting a functional impact on gene expression.

Gene→Variant (gene-first): 596:21 T > C 596:C instead of a T

Genes: 596

Variants: 21 T > C C instead of a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: + 21 T > C | Summary: The + 21 T > C substitution is hypothesized to lead to a more stable transcript, resulting in increased BCL2 protein levels, indicating a change in molecular function. Evidence Type: Oncogenic | Mutation: + 21 T > C | Summary: The increase in BCL2 protein levels associated with the + 21 T > C mutation suggests a contribution to tumor development or progression in ovarian cancer patients.

Gene→Variant (gene-first): 596:+ 21 T > C 596:C instead of a T

Genes: 596

Variants: + 21 T > C C instead of a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T to C | Summary: The mutation T to C at location 21 alters molecular function by increasing protein levels in vitro.

Gene→Variant (gene-first): 596:T to C

Genes: 596

Variants: T to C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T > C | Summary: The T > C mutation is associated with altered molecular function, specifically increasing the stability of BCL2 mRNA transcripts.

Gene→Variant (gene-first): 596:T > C

Genes: 596

Variants: T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T > C | Summary: The T > C variant was shown to significantly increase BCL2 expression levels, indicating an alteration in molecular function related to transcript stability. Evidence Type: Functional | Mutation: +21 C | Summary: The +21 C variant was part of the experimental validation that assessed its effect on BCL2 expression, suggesting a role in altering molecular function. Evidence Type: Functional | Mutation: +23 C > T | Summary: The +23 C > T variant was included in the study to evaluate its impact on BCL2 expression, indicating a potential alteration in molecular function.

Gene→Variant (gene-first): 596:+21 C 596:+21 T 728378:+23 C > T 596:T > C

Genes: 596 728378

Variants: +21 C +21 T +23 C > T T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C to T | Summary: The C to T mutation at location 21 in BCL2 alters the molecular function by stabilizing the BCL2 RNA secondary structure in vitro.

Gene→Variant (gene-first): 596:C to T

Genes: 596

Variants: C to T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C > T | Summary: The C > T change in BCL2 is assessed for its potential to alter mRNA structural ensemble, indicating a possible functional impact on molecular behavior. Evidence Type: Functional | Mutation: T > C | Summary: The T > C variant at position 21 shows a significant structural change as indicated by a lower p-value, suggesting it alters molecular function. Evidence Type: Functional | Mutation: + 21 T > C | Summary: The + 21 T > C variant is compared with adjacent variations and is evaluated for its structural consequences, indicating a potential functional alteration. Evidence Type: Functional | Mutation: + 23 C > T | Summary: The + 23 C > T variant is tested as a control and shows an insignificant change in structure, indicating it does not alter molecular function significantly.

Gene→Variant (gene-first): 596:+ 21 T > C 728378:+ 23 C > T 596:C > T 596:T > C 596:T at position 21

Genes: 596 728378

Variants: + 21 T > C + 23 C > T C > T T > C T at position 21

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T >C | Summary: The T >C variant at location 21 of BCL2 alters its RNA secondary structure, indicating a change in molecular function.

Gene→Variant (gene-first): 596:T >C

Genes: 596

Variants: T >C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: T instead of a C | Summary: The variant T instead of a C correlates with patient resistance to paclitaxel, allowing for retrospective prediction of treatment response and the number of treatment lines received. Evidence Type: Predictive | Mutation: rs1801018 | Summary: The variant rs1801018 is associated with resistance to paclitaxel, indicating its predictive value for treatment response in patients.

Gene→Variant (gene-first): 596:T instead of a C 596:rs1801018

Genes: 596

Variants: T instead of a C rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: + 21 T > C | Summary: The mutation from C to T at location 21 of BCL2 is associated with resistance to the chemotherapy drug paclitaxel, indicating its predictive value for treatment response. Evidence Type: Oncogenic | Mutation: + 21 T > C | Summary: The transition from C to T at location 21 of BCL2 contributes to tumor development or progression, highlighting its oncogenic potential.

Gene→Variant (gene-first): 596:+ 21 T > C 596:C to a T

Genes: 596

Variants: + 21 T > C C to a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 5

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 81027:rs6070697

Genes: 81027

Variants: rs6070697

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: T > C variation at position 21 | Summary: The T > C variation at position 21 of the BCL2 sequence is associated with predicting response to the chemotherapy drug paclitaxel.

Gene→Variant (gene-first): 596:T > C variation at position 21

Genes: 596

Variants: T > C variation at position 21

[Paper-level Aggregated] PMCID: PMC6478919

Evidence Type(s): Predictive, Functional, Prognostic

Justification: Predictive: The variation at position 21 of the BCL2 sequence (+21 T > C) predicts response to paclitaxel treatment, as patients with the T variant showed resistance while those with the C variant were more likely to respond. Functional: The T > C variant at location 21 of BCL2 alters RNA secondary structure and increases transcript stability, leading to higher BCL2 protein levels, which is functionally relevant in the context of treatment response. Prognostic: The presence of the T variant at location 21 is associated with a poorer treatment outcome, as indicated by the higher percentage of patients with this variant who required multiple lines of therapy compared to those with the C variant.

Gene→Variant (gene-first): BCL2(596):(AUC) of 39 BCL2(596):rs1801018 BCL2(596):+ 21 T > C POTEF(728378):+ 23 C > T BCL2(596):C > T BCL2(596):T > C BCL2(596):T at position 21 BCL2(596):C instead of a T BCL2(596):C to a T BCL2(596):+21 C BCL2(596):+21 T POTEF(728378):+23 C > T BCL2(596):21 T > C BCL2(596):C to T BCL2(596):T > C variation at position 21 BCL2(596):T >C BCL2(596):T instead of a C BCL2(596):T to C TUBB1(81027):rs6070697

Genes: BCL2(596) POTEF(728378) TUBB1(81027)

Variants: (AUC) of 39 rs1801018 + 21 T > C + 23 C > T C > T T > C T at position 21 C instead of a T C to a T +21 C +21 T +23 C > T 21 T > C C to T T > C variation at position 21 T >C T instead of a C T to C rs6070697

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 28

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the association between the rs1801018 variant and response to different treatments, indicating a correlation with treatment sensitivity.

Gene→Variant (gene-first): 596:(AUC) of 39 596:rs1801018

Genes: 596

Variants: (AUC) of 39 rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 26

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the study of BCL2 spatial expression patterns in relation to paclitaxel resistance, indicating a potential correlation between the 21 T > C variant and treatment response. Functional: The passage describes an immunofluorescence assay that assesses the localization patterns of the BCL2 variant, indicating an alteration in molecular function related to protein localization.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 25

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the variant 21 T > C leads to higher BCL2 expression, which is associated with resistance to the therapy paclitaxel. Oncogenic: The variant 21 T > C is implicated in contributing to tumor behavior by leading to increased expression of BCL2, which is associated with resistance to treatment, indicating a role in tumor progression.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage indicates that the presence of the 21 T > C variant correlates with increased abundance of transcripts when treated with paclitaxel, suggesting a relationship with treatment response. Functional: The mention of increased abundance of transcripts implies that the 21 T > C variant alters molecular function, likely affecting gene expression in response to paclitaxel.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 22

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the in vitro sensitivity to paclitaxel in relation to the 21 T > C variant, indicating that this variant may influence the response to the therapy. Functional: The variant is shown to alter the stability of the BCL2 transcript, which may lead to higher protein levels, indicating a change in molecular function.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the 21 T > C variant may regulate the transcriptional activity of the BCL2 gene, indicating an alteration in molecular function as evidenced by the increase in BCL2 mRNA levels in lymphocytes.

Gene→Variant (gene-first): 596:21 T > C 596:C instead of a T

Genes: 596

Variants: 21 T > C C instead of a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the + 21 T > C substitution alters BCL2 protein levels, indicating a change in molecular function due to the variant. Oncogenic: The context of the study involves ovarian cancer patients, and the variant is associated with increased BCL2 protein levels, which can contribute to tumor development or progression.

Gene→Variant (gene-first): 596:+ 21 T > C 596:C instead of a T

Genes: 596

Variants: + 21 T > C C instead of a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Justification: Functional: The passage indicates that changing T to C at a specific location alters protein levels, which demonstrates a change in molecular function.

Gene→Variant (gene-first): 596:T to C

Genes: 596

Variants: T to C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the T > C variant alters the stability of BCL2 mRNA transcripts, indicating a change in molecular function.

Gene→Variant (gene-first): 596:T > C

Genes: 596

Variants: T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Justification: Functional: The passage discusses how sequence modifications of BCL2 variants affect transcript stability and expression levels, indicating that the variants alter molecular function.

Gene→Variant (gene-first): 596:+21 C 596:+21 T 728378:+23 C > T 596:T > C

Genes: 596 728378

Variants: +21 C +21 T +23 C > T T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The variant C to T alters the molecular function by stabilizing the BCL2 RNA secondary structure, as indicated by the in vitro analysis.

Gene→Variant (gene-first): 596:C to T

Genes: 596

Variants: C to T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the C > T change in BCL2 alters the mRNA structural ensemble, indicating that the variant affects molecular function related to RNA structure.

Gene→Variant (gene-first): 596:+ 21 T > C 728378:+ 23 C > T 596:C > T 596:T > C 596:T at position 21

Genes: 596 728378

Variants: + 21 T > C + 23 C > T C > T T > C T at position 21

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the T > C variant alters the RNA secondary structure of BCL2, which is a change in molecular function.

Gene→Variant (gene-first): 596:T >C

Genes: 596

Variants: T >C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses how the variant rs1801018 correlates with patient resistance to paclitaxel, indicating its predictive value for treatment response. Diagnostic: The variation is associated with the classification of patients based on their treatment response, helping to define which patients are likely to respond to single or multiple lines of therapy.

Gene→Variant (gene-first): 596:T instead of a C 596:rs1801018

Genes: 596

Variants: T instead of a C rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive

Justification: Predictive: The passage indicates that the variant + 21 T > C is associated with resistance to paclitaxel, which correlates the variant with treatment response.

Gene→Variant (gene-first): 596:+ 21 T > C 596:C to a T

Genes: 596

Variants: + 21 T > C C to a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic

Justification: Diagnostic: The variant rs6070697 is discussed in the context of its distribution among treatment groups and its presence in both patients and controls, indicating its association with the study population and suggesting a role in defining or classifying the patient cohort.

Gene→Variant (gene-first): 81027:rs6070697

Genes: 81027

Variants: rs6070697

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive

Justification: Predictive: The passage states that the T > C variation at position 21 of the BCL2 sequence predicts response to paclitaxel, indicating a correlation with treatment response.

Gene→Variant (gene-first): 596:T > C variation at position 21

Genes: 596

Variants: T > C variation at position 21