[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Functional

Summary: Mutation: K700E | Summary: The K700E mutation is associated with distinct alternative splicing events and altered molecular functions in myelodysplastic syndromes (MDS). Splicing analysis suggests that this variant may influence molecular or biochemical functions related to splicing and mRNA processing.

Evidence Type: Functional Mutation: E862K | Summary: The SETBP1 E862K mutation is mentioned in the context of transformation, indicating a potential alteration in molecular function related to disease evolution.

Gene→Variant (gene-first): SF3B1(23451):K700E SETBP1(26040):E862K

Genes: SF3B1(23451) SETBP1(26040)

Variants: K700E E862K

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Oncogenic

Summary: Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with tumor development and progression in myelodysplastic syndromes (MDS). It is noted as the most frequent mutation in patients and contributes to improved overall survival outcomes, indicating its role in tumor development. The mutation influences alternative splicing events and is linked to specific clinical features, including a higher percentage of ring sideroblasts. Additionally, it was acquired during the transformation to AML, further suggesting its involvement in tumor progression.

Evidence Type: Oncogenic Mutation: R625 | Summary: The R625 mutation is part of recurrent non-K700E mutations associated with MDS, suggesting its contribution to tumor development or progression. The R625C variant is specifically associated with clonal evolution in patients with MDS-EB, indicating its role in tumor development.

Evidence Type: Oncogenic

Gene→Variant (gene-first): SF3B1(23451):K700E SF3B1(23451):R625

Genes: SF3B1(23451)

Variants: K700E R625

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Prognostic

Summary: Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with a favorable prognosis in myelodysplastic syndromes (MDS), correlating with significantly better overall survival (OS) outcomes compared to non-K700E mutations and SF3B1 wild-type patients. It is linked to specific clinical features, such as a higher percentage of ring sideroblasts and lower comprehensive cytogenetic scoring system (CCSS) scores, indicating its relevance in predicting disease outcomes. However, some evidence suggests that the K700E mutation may not show significant differences in OS compared to other SF3B1 mutations, indicating variability in its prognostic significance.

Evidence Type: Prognostic Mutation: R625 | Summary: The presence of the R625 mutation, as a recurrent mutation in MDS, may correlate with disease outcomes in patients, independent of therapy.

Gene→Variant (gene-first): SF3B1(23451):K700E SF3B1(23451):R625

Genes: SF3B1(23451)

Variants: K700E R625

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Diagnostic

Summary: Mutation: K700E | Summary: The K700E mutation in SF3B1 is important for diagnostic classification in myelodysplastic syndromes (MDS). It is used to refine sub-classification and risk assessment criteria, helping to define disease characteristics and classify patients based on specific clinico-pathologic features and cytogenetic aberrations. The presence of K700E aids in distinguishing between different subtypes of MDS and correlates with certain clinical features, such as a higher percentage of ring sideroblasts and ANC.

Gene→Variant (gene-first): SF3B1(23451):K700E

Genes: SF3B1(23451)

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: R625C | Summary: The SF3B1 R625C mutation is associated with clonal evolution in patients with MDS-EB, indicating its contribution to tumor development. Evidence Type: Oncogenic | Mutation: K700E | Summary: The SF3B1 K700E mutation was acquired during the transformation to AML, suggesting its role in tumor progression. Evidence Type: Functional | Mutation: E862K | Summary: The SETBP1 E862K mutation is mentioned in the context of transformation, indicating a potential alteration in molecular function related to disease evolution.

Gene→Variant (gene-first): 26040:E862K 23451:K700E 23451:R625C

Genes: 26040 23451

Variants: E862K K700E R625C

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 21

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The presence of the SF3B1 K700E mutation is associated with worse overall survival (OS) outcomes in the MDS cohort, indicating its role as an independent prognostic factor.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E SF3B1 mutation in low-grade MDS is associated with a trend for longer overall survival compared to non-K700E SF3B1 mutations, indicating a potential prognostic significance.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 19

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with significantly better overall survival (OS) compared to SF3B1 wild-type MDS, indicating its potential prognostic value in disease outcomes.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 18

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1mut MDS is associated with a significantly improved overall survival (OS) compared to non-K700E patients, indicating its prognostic relevance in disease outcome.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 17

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E SF3B1 mutation does not show significant differences in overall survival (OS) compared to other SF3B1 mutations, indicating it may not correlate with disease outcome independent of therapy.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 16

Evidence Type(s): Prognostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with significantly better overall survival (OS) outcomes in MDS patients compared to SF3B1 wild-type patients, indicating its prognostic value. Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation contributes to tumor development or progression in MDS, as evidenced by its association with improved survival outcomes in patients with this mutation compared to those without.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The SF3B1 K700E mutation is associated with distinct alternative splicing events and altered molecular functions in myelodysplastic syndromes (MDS), indicating its role in splicing and mRNA processing. Evidence Type: Oncogenic | Mutation: K700E | Summary: The SF3B1 K700E mutation contributes to tumor development and progression in myelodysplastic syndromes (MDS) by influencing the frequency and type of alternative splicing events.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The passage suggests that splicing analysis is being conducted to compare the K700E mutation with non-K700E mutated MDS, indicating that the K700E variant may alter molecular or biochemical function related to splicing.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 12

Evidence Type(s): Prognostic, Diagnostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with lower comprehensive cytogenetic scoring system (CCSS) scores, indicating a potential correlation with disease outcome in patients. Evidence Type: Diagnostic | Mutation: K700E | Summary: The presence of the K700E mutation helps classify patients into different categories based on their cytogenetic aberrations, distinguishing them from non-K700E MDS patients.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 11

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 10

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The K700E mutation is associated with specific clinico-pathologic features that help classify and define the subtype of MDS in patients. Evidence Type: Prognostic | Mutation: K700E | Summary: The presence of the K700E mutation correlates with certain clinical features, such as a higher percentage of ring sideroblasts and ANC, which may indicate disease outcome independent of therapy. Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation contributes to the development and progression of MDS, as indicated by its association with specific clinical features and classifications.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The comparison between SF3B1 K700E and non-K700E mutated MDS suggests that the K700E variant may be used to classify or define a subtype of myelodysplastic syndromes (MDS).

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is noted as the most frequent mutation in patients, indicating its contribution to tumor development in myelodysplastic syndromes (MDS).

Gene→Variant (gene-first): 23451:K666 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The K700E mutation is mentioned in the context of defining and classifying subtypes of MDS, indicating its role in diagnostic criteria.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 12

Evidence Type(s): Prognostic, Diagnostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with a favorable prognosis in myelodysplastic syndromes, indicating its relevance in predicting disease outcomes. Evidence Type: Diagnostic | Mutation: K700E | Summary: The K700E mutation is used to refine the sub-classification and risk assessment criteria for myelodysplastic syndromes, highlighting its role in defining disease characteristics.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with significantly better overall survival (OS) in patients with myelodysplastic syndromes (MDS) compared to non-K700E mutations, indicating its prognostic value. Evidence Type: Diagnostic | Mutation: K700E | Summary: The presence of the K700E mutation in SF3B1 is important for risk-assessment in myelodysplastic syndromes (MDS), suggesting its role in classifying the disease.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation is associated with superior overall survival in patients with MDS, indicating its role in tumor development or progression. Evidence Type: Prognostic | Mutation: K700E | Summary: The presence of the K700E mutation correlates with improved overall survival outcomes in MDS patients compared to those without this mutation. Evidence Type: Oncogenic | Mutation: R625 | Summary: The R625 mutation is part of recurrent non-K700E mutations associated with MDS, suggesting its contribution to tumor development or progression. Evidence Type: Prognostic | Mutation: R625 | Summary: The presence of R625, as a recurrent mutation, may correlate with disease outcomes in MDS patients, independent of therapy.

Gene→Variant (gene-first): 23451:K666 23451:K700 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Prognostic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The passage discusses the analysis of clinical-pathologic features and outcomes in MDS patients, indicating that K700E is used to explore differences in disease characteristics, which supports its role in diagnostic classification. Evidence Type: Prognostic | Mutation: K700E | Summary: The mention of outcomes in the context of K700E suggests that this variant may correlate with disease outcomes, supporting its prognostic significance in treatment-naive MDS patients.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with a favorable prognosis in myelodysplastic syndromes (MDS).

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Prognostic, Oncogenic, Functional

Justification: Prognostic: The text indicates that SF3B1 mutations, particularly K700E, are associated with a favorable prognosis in myelodysplastic syndromes (MDS), as evidenced by superior overall survival (OS) rates compared to SF3B1 wild-type patients. Oncogenic: The presence of SF3B1 mutations, including K700E and R625C, is implicated in the pathogenesis of myelodysplastic syndromes, suggesting their role as oncogenic drivers in this context. Functional: The analysis of splicing events and gene expression profiles between K700E and non-K700E SF3B1 mutations indicates functional differences that may impact disease characteristics and outcomes in MDS.

Gene→Variant (gene-first): SETBP1(26040):E862K SF3B1(23451):K700E SF3B1(23451):R625C SF3B1(23451):K666 SF3B1(23451):K700 SF3B1(23451):R625

Genes: SETBP1(26040) SF3B1(23451)

Variants: E862K K700E R625C K666 K700 R625

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the acquisition of the SF3B1 R625C, K700E, and SETBP1 E862K mutations during disease evolution, indicating their role in tumor development and progression in the context of MDS-EB transforming to AML. Functional: The mention of the SF3B1 mutations leading to changes in bone marrow morphology, such as the appearance of ring sideroblasts, suggests that these variants alter molecular or biochemical function related to the disease.

Gene→Variant (gene-first): 26040:E862K 23451:K700E 23451:R625C

Genes: 26040 23451

Variants: E862K K700E R625C

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 21

Evidence Type(s): Prognostic

Justification: Prognostic: The passage discusses the absence of the SF3B1 K700E mutation as an independent predictor of worse overall survival (OS), indicating a correlation between the variant and disease outcome.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that K700E SF3B1mut MDS showed a trend for longer overall survival (OS) compared to non-K700E SF3B1mut MDS, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The passage discusses the classification of K700E SF3B1mut MDS in relation to the proposed 2020 IWG-PM criteria, indicating its use in defining or classifying a disease subtype.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 19

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that K700E SF3B1mut MDS is associated with significantly better overall survival (OS) compared to SF3B1wt MDS, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The mention of K700E in the context of classifying MDS subtypes (e.g., comparing K700E SF3B1mut MDS to non-K700E SF3B1mut MDS) supports its role in defining or classifying a disease or subtype.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 18

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the overall survival (OS) rates of K700E SF3B1mut MDS patients compared to non-K700E patients, indicating a correlation with disease outcome independent of therapy. Diagnostic: The mention of K700E SF3B1mut MDS patients in relation to non-K700E patients suggests a classification or association with a specific disease subtype.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 17

Evidence Type(s): Prognostic

Justification: Prognostic: The passage discusses overall survival (OS) in relation to the K700E variant, indicating that it correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 16

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the overall survival (OS) outcomes of K700E SF3B1mut MDS patients compared to SF3B1wt patients, indicating that the K700E variant correlates with better disease outcomes independent of therapy. Diagnostic: The K700E variant is used to classify and differentiate between SF3B1mut and SF3B1wt MDS patients, indicating its role in defining disease subtypes.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the impact of the SF3B1 K700E variant on alternative splicing events, indicating that it alters molecular function related to splicing and gene expression. Oncogenic: The SF3B1 K700E variant is associated with mutated myelodysplastic syndromes (MDS), suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Justification: Functional: The passage discusses splicing analysis related to the K700E variant, indicating an alteration in molecular function.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 12

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the classification of patients based on the presence of the K700E variant, indicating its association with lower CCSS scores, which suggests a role in defining or classifying a disease subtype. Oncogenic: The mention of the K700E variant in the context of patients with MDS (myelodysplastic syndromes) implies its contribution to tumor development or progression, as it is associated with specific cytogenetic aberrations.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 11

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 10

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the clinico-pathologic features of MDS patients with K700E mutations, indicating that these mutations are associated with specific disease characteristics and classifications, such as higher percentages of ring sideroblasts and differences in IPSS-R categories. Oncogenic: The K700E mutation in SF3B1 is implicated in the classification of MDS patients and is associated with specific tumor characteristics, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 9

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the frequency of specific mutations, including K666, K700E, and R625, in patients with MDS, indicating their association with the disease and their role in defining the mutational landscape. Oncogenic: The mention of SF3B1 mutations, including K700E, K666, and R625, as frequent mutations in patients with MDS suggests that these somatic variants contribute to tumor development or progression in this context.

Gene→Variant (gene-first): 23451:K666 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the mutational landscape of SF3B1 mutations, specifically mentioning the K700E subtype, which indicates its role in classifying or defining a disease subtype. Oncogenic: The mention of K700E in the context of SF3B1 mutations suggests its contribution to tumor development or progression, as it is associated with a specific subtype of myelodysplastic syndromes (MDS).

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 12

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage discusses how MDS with SF3B1 K700E mutations can be used to refine sub-classification and risk assessment criteria, indicating its role in defining or classifying a disease subtype. Prognostic: The passage states that MDS with SF3B1 K700E mutations is regarded to have a favorable prognosis, which correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that SF3B1 K700E mutated MDS shows significantly better overall survival (OS) compared to non-K700E mutations, suggesting a correlation with disease outcome. Diagnostic: The mention of distinct clinicopathological and genomic characteristics associated with K700E and non-K700E SF3B1 mutations implies that the mutation type is used for risk-assessment and classification of MDS.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of K700E and non-K700E mutations with specific patient characteristics and outcomes, indicating their role in classifying patients with MDS. Prognostic: The passage reports on overall survival outcomes associated with SF3B1 mutations, including K700E, indicating that these variants correlate with disease prognosis independent of therapy. Oncogenic: The mention of mutations such as K700E contributing to the classification of MDS and their association with specific patient outcomes suggests a role in tumor development or progression.

Gene→Variant (gene-first): 23451:K666 23451:K700 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the analysis of clinical-pathologic features and outcomes in MDS patients, specifically exploring differences between K700E and non-K700E variants, indicating a potential role in classification or association with disease characteristics. Oncogenic: The mention of analyzing the clinical-pathologic features of SF3B1mut patients, including K700E, suggests that this variant may contribute to tumor development or progression in the context of MDS.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage states that SF3B1 mutations, including K700E, have a favorable prognosis in myelodysplastic syndromes, indicating a correlation with disease outcome. Diagnostic: The mention of SF3B1 mutations in the context of myelodysplastic syndromes suggests that these mutations, including K700E, are used to classify or define the disease.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the acquisition of the SF3B1 R625C, K700E, and SETBP1 E862K mutations during disease evolution, indicating their role in tumor development and progression in the context of MDS-EB transforming to AML. Functional: The mention of the SF3B1 mutations leading to changes in bone marrow morphology, such as the appearance of ring sideroblasts, suggests that these variants alter molecular or biochemical function related to the disease.

Gene→Variant (gene-first): 26040:E862K 23451:K700E 23451:R625C

Genes: 26040 23451

Variants: E862K K700E R625C

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 21

Evidence Type(s): Prognostic

Justification: Prognostic: The passage discusses the absence of the SF3B1 K700E mutation as an independent predictor of worse overall survival (OS), indicating a correlation between the variant and disease outcome.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that K700E SF3B1mut MDS showed a trend for longer overall survival (OS) compared to non-K700E SF3B1mut MDS, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The passage discusses the classification of K700E SF3B1mut MDS in relation to the proposed 2020 IWG-PM criteria, indicating its use in defining or classifying a disease subtype.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 19

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that K700E SF3B1mut MDS is associated with significantly better overall survival (OS) compared to SF3B1wt MDS, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The mention of K700E in the context of classifying MDS subtypes (e.g., comparing K700E SF3B1mut MDS to non-K700E SF3B1mut MDS) supports its role in defining or classifying a disease or subtype.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 18

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the overall survival (OS) rates of K700E SF3B1mut MDS patients compared to non-K700E patients, indicating a correlation with disease outcome independent of therapy. Diagnostic: The mention of K700E SF3B1mut MDS patients in relation to non-K700E patients suggests a classification or association with a specific disease subtype.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 17

Evidence Type(s): Prognostic

Justification: Prognostic: The passage discusses overall survival (OS) in relation to the K700E variant, indicating that it correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 16

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the overall survival (OS) outcomes of K700E SF3B1mut MDS patients compared to SF3B1wt patients, indicating that the K700E variant correlates with better disease outcomes independent of therapy. Diagnostic: The K700E variant is used to classify and differentiate between SF3B1mut and SF3B1wt MDS patients, indicating its role in defining disease subtypes.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the impact of the SF3B1 K700E variant on alternative splicing events, indicating that it alters molecular function related to splicing and gene expression. Oncogenic: The SF3B1 K700E variant is associated with mutated myelodysplastic syndromes (MDS), suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Justification: Functional: The passage discusses splicing analysis related to the K700E variant, indicating an alteration in molecular function.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 12

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the classification of patients based on the presence of the K700E variant, indicating its association with lower CCSS scores, which suggests a role in defining or classifying a disease subtype. Oncogenic: The mention of the K700E variant in the context of patients with MDS (myelodysplastic syndromes) implies its contribution to tumor development or progression, as it is associated with specific cytogenetic aberrations.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 11

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 10

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the clinico-pathologic features of MDS patients with K700E mutations, indicating that these mutations are associated with specific disease characteristics and classifications, such as higher percentages of ring sideroblasts and differences in IPSS-R categories. Oncogenic: The K700E mutation in SF3B1 is implicated in the classification of MDS patients and is associated with specific tumor characteristics, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 9

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the frequency of specific mutations, including K666, K700E, and R625, in patients with MDS, indicating their association with the disease and their role in defining the mutational landscape. Oncogenic: The mention of SF3B1 mutations, including K700E, K666, and R625, as frequent mutations in patients with MDS suggests that these somatic variants contribute to tumor development or progression in this context.

Gene→Variant (gene-first): 23451:K666 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the mutational landscape of SF3B1 mutations, specifically mentioning the K700E subtype, which indicates its role in classifying or defining a disease subtype. Oncogenic: The mention of K700E in the context of SF3B1 mutations suggests its contribution to tumor development or progression, as it is associated with a specific subtype of myelodysplastic syndromes (MDS).

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 12

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage discusses how MDS with SF3B1 K700E mutations can be used to refine sub-classification and risk assessment criteria, indicating its role in defining or classifying a disease subtype. Prognostic: The passage states that MDS with SF3B1 K700E mutations is regarded to have a favorable prognosis, which correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that SF3B1 K700E mutated MDS shows significantly better overall survival (OS) compared to non-K700E mutations, suggesting a correlation with disease outcome. Diagnostic: The mention of distinct clinicopathological and genomic characteristics associated with K700E and non-K700E SF3B1 mutations implies that the mutation type is used for risk-assessment and classification of MDS.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of K700E and non-K700E mutations with specific patient characteristics and outcomes, indicating their role in classifying patients with MDS. Prognostic: The passage reports on overall survival outcomes associated with SF3B1 mutations, including K700E, indicating that these variants correlate with disease prognosis independent of therapy. Oncogenic: The mention of mutations such as K700E contributing to the classification of MDS and their association with specific patient outcomes suggests a role in tumor development or progression.

Gene→Variant (gene-first): 23451:K666 23451:K700 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the analysis of clinical-pathologic features and outcomes in MDS patients, specifically exploring differences between K700E and non-K700E variants, indicating a potential role in classification or association with disease characteristics. Oncogenic: The mention of analyzing the clinical-pathologic features of SF3B1mut patients, including K700E, suggests that this variant may contribute to tumor development or progression in the context of MDS.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage states that SF3B1 mutations, including K700E, have a favorable prognosis in myelodysplastic syndromes, indicating a correlation with disease outcome. Diagnostic: The mention of SF3B1 mutations in the context of myelodysplastic syndromes suggests that these mutations, including K700E, are used to classify or define the disease.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E