[Paper-level Aggregated] PMCID: PMC4398541

Evidence Type(s): Functional

Summary: Mutation: L23F | Summary: The L23F mutation showed increased nuclear localization of PTEN and displayed compromised/partial PIP3 catalytic activity in yeast, indicating alterations in molecular function related to subcellular localization and enzymatic activity.

Evidence Type: Functional Mutation: M35R | Summary: The M35R mutation demonstrated increased nuclear localization of PTEN and resulted in a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: G36R | Summary: The G36R mutation resulted in increased nuclear localization of PTEN and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: K13E | Summary: The K13E mutation fully abrogated the nuclear accumulation of PTEN 1-375 and resulted in a total loss of phosphatase activity in vivo, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: A34D | Summary: The A34D mutation fully abrogated the nuclear accumulation of PTEN 1-375 and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: L42P | Summary: The L42P mutation fully abrogated the nuclear accumulation of PTEN 1-375 and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: R15I | Summary: The R15I mutation caused a partial inhibition of nuclear accumulation of PTEN and resulted in a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: R15S | Summary: The R15S mutation resulted in a partial inhibition of nuclear accumulation of PTEN and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: D24Y | Summary: The D24Y mutation caused a partial inhibition of nuclear accumulation of PTEN and resulted in a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: I33S | Summary: The I33S mutation resulted in a partial inhibition of nuclear accumulation of PTEN and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: S10N | Summary: The S10N mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN and partially reduced PTEN activity in a yeast model, suggesting no functional change.

Evidence Type: Functional Mutation: Y16C | Summary: The Y16C mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN and partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function.

Evidence Type: Functional Mutation: A34V | Summary: The A34V mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN and partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function.

Evidence Type: Functional Mutation: A39V | Summary: The A39V mutation alters the nuclear accumulation of PTEN and resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, suggesting it alters molecular function.

Evidence Type: Functional Mutation: D19A | Summary: The D19A mutation affects the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: G20A | Summary: The G20A mutation influences the cytoplasmic localization of PTEN, indicating a change in its molecular function.

Evidence Type: Functional Mutation: F21A | Summary: The F21A mutation impacts the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: K13A | Summary: The K13A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization.

Evidence Type: Functional Mutation: R14A | Summary: The R14A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: R15A | Summary: The R15A mutation inhibits nuclear entry of PTEN and resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: E18A | Summary: The E18A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: D24A | Summary: The D24A mutation inhibits nuclear entry of PTEN and led to a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function.

Evidence Type: Functional Mutation: Y16A | Summary: The Y16A mutation inhibits nuclear entry of PTEN and displayed a complete loss-of-function in PTEN's PIP3 phosphatase activity, suggesting it alters molecular function.

Evidence Type: Functional Mutation: Y27A | Summary: The Y27A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function.

Evidence Type: Functional Mutation: I28A | Summary: The I28A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: N31A | Summary: The N31A mutation inhibits nuclear entry of PTEN and did not affect PIP3 catalytic activity in yeast, suggesting a change in molecular function.

Evidence Type: Functional Mutation: I32A | Summary: The I32A mutation inhibits nuclear entry of PTEN and resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, reflecting an alteration in molecular function.

Evidence Type: Functional Mutation: I33A | Summary: The I33A mutation inhibits nuclear entry of PTEN and partially compromised PTEN activity, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: P30A | Summary: The P30A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: N12A | Summary: The N12A mutation inhibits nuclear accumulation of PTEN, indicating a change in its molecular function.

Evidence Type: Functional Mutation: M35A | Summary: The M35A mutation inhibits nuclear accumulation of PTEN and caused a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function.

Evidence Type: Functional Mutation: L42A | Summary: The L42A mutation abrogated both nuclear accumulation and PIP3 phosphatase activity of PTEN, indicating a change in molecular function.

Evidence Type: Functional Mutation: K13R | Summary: The K13R mutation alters the nuclear localization of PTEN and enhances its ability to counteract PI3K activity in a yeast model.

Evidence Type: Functional Mutation: R14K | Summary: The R14K mutation affects the nuclear localization of PTEN and maintains its phosphatase activity in vivo.

Evidence Type: Functional Mutation: R15K | Summary: The R15K mutation increases the nuclear accumulation of PTEN but does not display phosphatase activity in vivo.

Gene→Variant (gene-first): PTEN(5728):L23F PTEN(5728):M35R PTEN(5728):G36R PTEN(5728):K13E PTEN(5728):A34D PTEN(5728):L42P PTEN(5728):R15I PTEN(5728):R15S PTEN(5728):D24Y PTEN(5728):I33S PTEN(5728):S10N PTEN(5728):Y16C PTEN(5728):A34V PTEN(5728):A39V ACTG1(71):D19A PTEN(5728):G20A PTEN(5728):F21A PTEN(5728):K13A AAA1(100329167):R14A PTEN(5728):R15A PTEN(5728):E18A PTEN(5728):D24A PTEN(5728):Y16A PTEN(5728):Y27A PTEN(5728):I28A PTEN(5728):N31A PTEN(5728):I32A PTEN(5728):I33A PTEN(5728):P30A PTEN(5728):N12A PTEN(5728):M35A PTEN(5728):L42A PTEN(5728):K13R AAA1(100329167):R14K PTEN(5728):R15K

Genes: PTEN(5728) ACTG1(71) AAA1(100329167)

Variants: L23F M35R G36R K13E A34D L42P R15I R15S D24Y I33S S10N Y16C A34V A39V D19A G20A F21A K13A R14A R15A E18A D24A Y16A Y27A I28A N31A I32A I33A P30A N12A M35A L42A K13R R14K R15K

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation displays compromised/partial PIP3 catalytic activity in yeast, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: N31A | Summary: The N31A mutation did not affect PIP3 catalytic activity in yeast but impaired the nuclear accumulation of PTEN 1-375 in mammalian cells, suggesting a change in molecular function.

Gene→Variant (gene-first): 5728:L23F 5728:N31A

Genes: 5728

Variants: L23F N31A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13R | Summary: The K13R mutation alters the nuclear localization of PTEN and enhances its ability to counteract PI3K activity in a yeast model. Evidence Type: Functional | Mutation: R14K | Summary: The R14K mutation affects the nuclear localization of PTEN and maintains its phosphatase activity in vivo. Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation results in a total loss of phosphatase activity in vivo. Evidence Type: Functional | Mutation: R15K | Summary: The R15K mutation increases the nuclear accumulation of PTEN but does not display phosphatase activity in vivo. Evidence Type: Functional | Mutation: K13A | Summary: The K13A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity. Evidence Type: Functional | Mutation: R14A | Summary: The R14A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity. Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity.

Gene→Variant (gene-first): 100329167:Arg14 5728:Arg15 5728:K13A 5728:K13E 5728:K13R 5728:Lys13 100329167:R14A 100329167:R14K 5728:R15A 5728:R15K

Genes: 100329167 5728

Variants: Arg14 Arg15 K13A K13E K13R Lys13 R14A R14K R15A R15K

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Y16A | Summary: The Y16A mutation displayed a complete loss-of-function in PTEN's PIP3 phosphatase activity, suggesting it alters molecular function. Evidence Type: Functional | Mutation: D24A | Summary: The D24A mutation led to a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function. Evidence Type: Functional | Mutation: I32A | Summary: The I32A mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, reflecting an alteration in molecular function. Evidence Type: Functional | Mutation: M35A | Summary: The M35A mutation caused a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function. Evidence Type: Functional | Mutation: A39V | Summary: The A39V mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, suggesting it alters molecular function. Evidence Type: Functional | Mutation: I33A | Summary: The I33A mutation partially compromised PTEN activity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: L42A | Summary: The L42A mutation abrogated both nuclear accumulation and PIP3 phosphatase activity of PTEN, indicating a change in molecular function.

Gene→Variant (gene-first): 5728:A39V 5728:D24A 5728:I32A 5728:I33A 5728:I5A 5728:K6A 5728:L42A 5728:M35A 5728:P38A 5728:Q17A 5728:R15A 5728:S10A 5728:Y16A

Genes: 5728

Variants: A39V D24A I32A I33A I5A K6A L42A M35A P38A Q17A R15A S10A Y16A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A39V | Summary: The A39V mutation alters the nuclear accumulation of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: D19A | Summary: The D19A mutation affects the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: G20A | Summary: The G20A mutation influences the cytoplasmic localization of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: F21A | Summary: The F21A mutation impacts the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: K13A | Summary: The K13A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: R14A | Summary: The R14A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: E18A | Summary: The E18A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: D24A | Summary: The D24A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: Y16A | Summary: The Y16A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: Y27A | Summary: The Y27A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: I28A | Summary: The I28A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: N31A | Summary: The N31A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: I32A | Summary: The I32A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: I33A | Summary: The I33A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: P30A | Summary: The P30A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: N12A | Summary: The N12A mutation inhibits nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: M35A | Summary: The M35A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function.

Gene→Variant (gene-first): 5728:A39V 5728:Ala residues were mutated to Val 71:D19A 5728:D24A 5728:E18A 5728:F21A 5728:G20A 5728:I28A 5728:I32A 5728:I33A 5728:K13A 5728:L42A 5728:M35A 5728:N12A 5728:N31A 5728:P30A 100329167:R14A 5728:R15A 5728:Y16A 5728:Y27A

Genes: 5728 71 100329167

Variants: A39V Ala residues were mutated to Val D19A D24A E18A F21A G20A I28A I32A I33A K13A L42A M35A N12A N31A P30A R14A R15A Y16A Y27A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: R15I | Summary: The R15I mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: D24Y | Summary: The D24Y mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: I33S | Summary: The I33S mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: A34D | Summary: The A34D mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: M35R | Summary: The M35R mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: G36R | Summary: The G36R mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: L42P | Summary: The L42P mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: S10N | Summary: The S10N mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: Y16C | Summary: The Y16C mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: A34V | Summary: The A34V mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation showed increased nuclear localization of PTEN, indicating an alteration in molecular function related to subcellular localization. Evidence Type: Functional | Mutation: M35R | Summary: The M35R mutation demonstrated increased nuclear localization of PTEN, suggesting a change in its molecular function. Evidence Type: Functional | Mutation: G36R | Summary: The G36R mutation resulted in increased nuclear localization of PTEN, reflecting an alteration in its molecular function. Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation fully abrogated the nuclear accumulation of PTEN 1-375, indicating a significant change in its molecular function. Evidence Type: Functional | Mutation: A34D | Summary: The A34D mutation fully abrogated the nuclear accumulation of PTEN 1-375, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: L42P | Summary: The L42P mutation fully abrogated the nuclear accumulation of PTEN 1-375, indicating a change in its molecular function. Evidence Type: Functional | Mutation: R15I | Summary: The R15I mutation caused a partial inhibition of nuclear accumulation of PTEN, reflecting an alteration in its molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S mutation resulted in a partial inhibition of nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: D24Y | Summary: The D24Y mutation caused a partial inhibition of nuclear accumulation of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: I33S | Summary: The I33S mutation resulted in a partial inhibition of nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: S10N | Summary: The S10N mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, suggesting no functional change. Evidence Type: Functional | Mutation: Y16C | Summary: The Y16C mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, indicating no functional change. Evidence Type: Functional | Mutation: A34V | Summary: The A34V mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, suggesting no functional change.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C

[Paper-level Aggregated] PMCID: PMC4398541

Evidence Type(s): Functional, Oncogenic, Predictive

Justification: Functional: The text describes a functional analysis of various PTEN mutations, assessing their impact on subcellular localization and PIP3 phosphatase activity, indicating their functional roles in PTEN's tumor suppressor activity. Oncogenic: The mutations are associated with tumorigenesis, as they are described as "tumor-associated" and their effects on PTEN function suggest a potential role in cancer development. Predictive: The analysis of specific mutations and their effects on PTEN activity and localization can predict the functional consequences of these mutations in a clinical context, potentially guiding therapeutic decisions.

Gene→Variant (gene-first): PTEN(5728):A34D PTEN(5728):A34V PTEN(5728):D24Y PTEN(5728):G36R PTEN(5728):I33S PTEN(5728):K13E PTEN(5728):L23F PTEN(5728):L42P PTEN(5728):M35R PTEN(5728):R15I PTEN(5728):R15S PTEN(5728):S10N PTEN(5728):Y16C PTEN(5728):A39V PTEN(5728):Ala residues were mutated to Val ACTG1(71):D19A PTEN(5728):D24A PTEN(5728):E18A PTEN(5728):F21A PTEN(5728):G20A PTEN(5728):I28A PTEN(5728):I32A PTEN(5728):I33A PTEN(5728):K13A PTEN(5728):L42A PTEN(5728):M35A PTEN(5728):N12A PTEN(5728):N31A PTEN(5728):P30A AAA1(100329167):R14A PTEN(5728):R15A PTEN(5728):Y16A PTEN(5728):Y27A PTEN(5728):I5A PTEN(5728):K6A PTEN(5728):P38A PTEN(5728):Q17A PTEN(5728):S10A AAA1(100329167):Arg14 PTEN(5728):Arg15 PTEN(5728):K13R PTEN(5728):Lys13 AAA1(100329167):R14K PTEN(5728):R15K

Genes: PTEN(5728) ACTG1(71) AAA1(100329167)

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C A39V Ala residues were mutated to Val D19A D24A E18A F21A G20A I28A I32A I33A K13A L42A M35A N12A N31A P30A R14A R15A Y16A Y27A I5A K6A P38A Q17A S10A Arg14 Arg15 K13R Lys13 R14K R15K

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the L23F and N31A mutations alter the molecular function of PTEN, specifically its PIP3 catalytic activity and nuclear accumulation, indicating changes in biochemical function. Oncogenic: The results indicate that the L23F mutation leads to a complete loss-of-function in terms of cell growth inhibitory capacity, suggesting that it contributes to tumor development or progression.

Gene→Variant (gene-first): 5728:L23F 5728:N31A

Genes: 5728

Variants: L23F N31A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how specific mutations (K13R, R14K, K13E, etc.) affect the molecular functions of PTEN, including its nuclear localization and phosphatase activity, indicating alterations in biochemical function. Oncogenic: The mutations are described in the context of their role in PTEN's function related to tumor development, particularly in terms of phosphatase activity and localization, which are critical for its tumor suppressor role.

Gene→Variant (gene-first): 100329167:Arg14 5728:Arg15 5728:K13A 5728:K13E 5728:K13R 5728:Lys13 100329167:R14A 100329167:R14K 5728:R15A 5728:R15K

Genes: 100329167 5728

Variants: Arg14 Arg15 K13A K13E K13R Lys13 R14A R14K R15A R15K

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how specific mutations alter PTEN's phosphatase activity and nuclear accumulation, indicating that these variants affect molecular function. Oncogenic: The context implies that the mutations contribute to the functional behavior of PTEN, which is known to be involved in tumor suppression, suggesting a role in tumor development or progression.

Gene→Variant (gene-first): 5728:A39V 5728:D24A 5728:I32A 5728:I33A 5728:I5A 5728:K6A 5728:L42A 5728:M35A 5728:P38A 5728:Q17A 5728:R15A 5728:S10A 5728:Y16A

Genes: 5728

Variants: A39V D24A I32A I33A I5A K6A L42A M35A P38A Q17A R15A S10A Y16A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Justification: Functional: The passage discusses how specific mutations in the PTEN N-terminal region alter its subcellular localization, indicating that these variants affect the molecular function of the protein.

Gene→Variant (gene-first): 5728:A39V 5728:Ala residues were mutated to Val 71:D19A 5728:D24A 5728:E18A 5728:F21A 5728:G20A 5728:I28A 5728:I32A 5728:I33A 5728:K13A 5728:L42A 5728:M35A 5728:N12A 5728:N31A 5728:P30A 100329167:R14A 5728:R15A 5728:Y16A 5728:Y27A

Genes: 5728 71 100329167

Variants: A39V Ala residues were mutated to Val D19A D24A E18A F21A G20A I28A I32A I33A K13A L42A M35A N12A N31A P30A R14A R15A Y16A Y27A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the mutations alter the PIP3 phosphatase activity of PTEN, indicating that these variants affect molecular function. Oncogenic: The variants are described as "tumor-associated" and their effects on PTEN activity suggest a contribution to tumor development or progression.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Justification: Functional: The passage discusses how various PTEN mutations alter the nuclear/cytosolic localization and function of the protein, indicating changes in molecular or biochemical function.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C