[Paper-level Aggregated] PMCID: PMC7190743

Evidence Type(s): Functional

Summary: Mutation: C124S | Summary: The C124S variant is characterized as catalytically inactive for both protein and lipid phosphatase functions, showing complete loss of function (LoF) indistinguishable from GFP controls in terms of PSD95 density. It alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype, and is involved in genetic interactions that alter PI3P metabolism, indicating a significant alteration in molecular function.

Evidence Type: Functional Mutation: G129E | Summary: The G129E variant is described as a lipid phosphatase-dead variant and alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype. It exhibited eclosion significantly faster than the empty vector control, suggesting a functional change in its activity.

Evidence Type: Functional Mutation: Y138L | Summary: Y138L is identified as a protein phosphatase-dead variant, indicating a change in the molecular function of the PTEN protein.

Evidence Type: Functional Mutation: N117S | Summary: The N117S variant slowed the developmental rate further than the wild-type, indicating a functional alteration in its role.

Evidence Type: Functional Mutation: Q298E | Summary: The Q298E variant also slowed the developmental rate further than the wild-type, suggesting a functional change in its activity.

Evidence Type: Functional Mutation: A79T | Summary: The A79T variant exhibited a gain-of-function (GoF) phenotype in axonal growth and altered PSD95 density and dendrite length, indicating a change in molecular function. It retained wild-type-like function in the context of chemotaxis assays in C. elegans.

Evidence Type: Functional Mutation: I101T | Summary: The I101T variant, along with C124S, increased soma size more than GFP, suggesting a change in molecular function related to neuronal growth.

Evidence Type: Functional Mutation: G132D | Summary: The G132D variant exhibited stronger negative chemotaxis than daf-18 mutants and increased soma size more than GFP, indicating a functional alteration associated with neuronal growth.

Evidence Type: Functional Mutation: D268E | Summary: The D268E variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms and appeared wild-type-like in all measures of growth and synaptogenesis, suggesting it does not alter molecular function significantly.

Evidence Type: Functional Mutation: T167N | Summary: The T167N variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms.

Evidence Type: Functional Mutation: Y176C | Summary: The Y176C variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms.

Evidence Type: Functional Mutation: H93Y | Summary: The H93Y variant is associated with altered molecular function, specifically reduced protein stability compared to wild-type PTEN.

Evidence Type: Functional Mutation: P354Q | Summary: The P354Q variant retained wild-type-like function in the context of chemotaxis assays in C. elegans and does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: R130L | Summary: The R130L variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence and does not show significant differences in protein stability compared to wild-type PTEN.

Evidence Type: Functional Mutation: R14G | Summary: The R14G variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: R15S | Summary: The R15S variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: T78A | Summary: The T78A variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: A126D | Summary: The A126D variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: A126P | Summary: The A126P variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: H123Q | Summary: The H123Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: P38H | Summary: The P38H variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: R130Q | Summary: The R130Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence.

Gene→Variant (gene-first): PTEN(5728):C124S PTEN(5728):G129E PTEN(5728):Y138L PTEN(5728):N117S PTEN(5728):Q298E PTEN(5728):A79T PTEN(5728):I101T PTEN(5728):G132D PTEN(5728):D268E PTEN(5728):T167N PTEN(5728):Y176C PTEN(5728):H93Y PTEN(5728):P354Q PTEN(5728):R130L PTEN(5728):R14G PTEN(5728):R15S PTEN(5728):T78A PTEN(5728):A126D PTEN(5728):A126P PTEN(5728):H123Q PTEN(5728):P38H PTEN(5728):R130Q

Genes: PTEN(5728)

Variants: C124S G129E Y138L N117S Q298E A79T I101T G132D D268E T167N Y176C H93Y P354Q R130L R14G R15S T78A A126D A126P H123Q P38H R130Q

[Paper-level Aggregated] PMCID: PMC7190743

Evidence Type(s): Oncogenic

Summary: Mutation: C124S | Summary: C124S has been found in somatic cancer, suggesting it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: R130X | Summary: R130X is associated with somatic cancer, indicating its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: R335X | Summary: R335X is commonly associated with somatic cancer, suggesting it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: P354Q | Summary: The variant P354Q is classified as Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: T202I | Summary: The variant T202I is classified as Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: T78A | Summary: The variant T78A is classified as Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: I135V | Summary: The variant I135V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N340H | Summary: The variant N340H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N356D | Summary: The variant N356D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: K402N | Summary: The variant K402N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N117S | Summary: The variant N117S is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: Y180H | Summary: The variant Y180H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: I203V | Summary: The variant I203V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: Q298E | Summary: The variant Q298E is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N340D | Summary: The variant N340D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: K342N | Summary: The variant K342N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: L345V | Summary: The variant L345V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: I400V | Summary: The variant I400V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Gene→Variant (gene-first): PTEN(5728):C124S PTEN(5728):R130X PTEN(5728):R335X PTEN(5728):P354Q PTEN(5728):T202I PTEN(5728):T78A PTEN(5728):I135V PTEN(5728):N340H PTEN(5728):N356D PTEN(5728):K402N PTEN(5728):N117S PTEN(5728):Y180H PTEN(5728):I203V PTEN(5728):Q298E PTEN(5728):N340D PTEN(5728):K342N PTEN(5728):L345V PTEN(5728):I400V

Genes: PTEN(5728)

Variants: C124S R130X R335X P354Q T202I T78A I135V N340H N356D K402N N117S Y180H I203V Q298E N340D K342N L345V I400V

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 25

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: P354Q | Summary: The variant P354Q is classified as Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: T202I | Summary: The variant T202I is classified as Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: T78A | Summary: The variant T78A is classified as Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: I135V | Summary: The variant I135V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N340H | Summary: The variant N340H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N356D | Summary: The variant N356D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: K402N | Summary: The variant K402N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N117S | Summary: The variant N117S is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: Y180H | Summary: The variant Y180H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: I203V | Summary: The variant I203V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: Q298E | Summary: The variant Q298E is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N340D | Summary: The variant N340D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: K342N | Summary: The variant K342N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: L345V | Summary: The variant L345V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: I400V | Summary: The variant I400V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Gene→Variant (gene-first): 5728:A79T 5728:C211W 5728:E157G 5728:H123Q 5728:I135V 5728:I203V 5728:I400V 5728:K342N 5728:K402N 5728:L345V 5728:L70V 5728:M35V 5728:N117S 5728:N228S 5728:N340D 5728:N340H 5728:N356D 5728:P354Q 5728:Q298E 5728:S229T 5728:T202I 5728:T78A 5728:W274L 5728:Y176C 5728:Y180H 5728:Y65C

Genes: 5728

Variants: A79T C211W E157G H123Q I135V I203V I400V K342N K402N L345V L70V M35V N117S N228S N340D N340H N356D P354Q Q298E S229T T202I T78A W274L Y176C Y180H Y65C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A126D | Summary: The A126D variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: A126P | Summary: The A126P variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: H123Q | Summary: The H123Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: P38H | Summary: The P38H variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: R130L | Summary: The R130L variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: R130Q | Summary: The R130Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype. Evidence Type: Functional | Mutation: G129E | Summary: The G129E variant alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype.

Gene→Variant (gene-first): 5728:A126D 5728:A126P 5728:C124S 5728:G129E 5728:H123Q 5728:P354Q 5728:P38H 5728:Q396R 5728:R130L 5728:R130Q

Genes: 5728

Variants: A126D A126P C124S G129E H123Q P354Q P38H Q396R R130L R130Q

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: H93Y | Summary: The H93Y variant is associated with altered molecular function, specifically reduced protein stability compared to wild-type PTEN. Evidence Type: Functional | Mutation: P354Q | Summary: The P354Q variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: R130L | Summary: The R130L variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: R14G | Summary: The R14G variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: T78A | Summary: The T78A variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Gene→Variant (gene-first): 5728:H93Y 5728:P354Q 5728:R130L 5728:R14G 5728:R15S 5728:T78A

Genes: 5728

Variants: H93Y P354Q R130L R14G R15S T78A

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A79T | Summary: The A79T variant retained wild-type-like function in the context of chemotaxis assays in C. elegans. Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant exhibited complete loss of function (LoF) in the chemotaxis assays conducted in daf-18 mutant worms. Evidence Type: Functional | Mutation: D268E | Summary: The D268E variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms. Evidence Type: Functional | Mutation: G132D | Summary: The G132D variant exhibited stronger negative chemotaxis than daf-18 mutants, indicating a functional alteration. Evidence Type: Functional | Mutation: P354Q | Summary: The P354Q variant retained wild-type-like function in the context of chemotaxis assays in C. elegans. Evidence Type: Functional | Mutation: T167N | Summary: The T167N variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms. Evidence Type: Functional | Mutation: Y176C | Summary: The Y176C variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:P354Q 5728:T167N 5728:Y176C

Genes: 5728

Variants: A79T C124S D268E G132D P354Q T167N Y176C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A79T | Summary: The A79T variant exhibited a gain-of-function (GoF) phenotype in axonal growth and altered PSD95 density and dendrite length, indicating a change in molecular function. Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant showed complete loss of function (LoF) indistinguishable from GFP controls in terms of PSD95 density, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: I101T | Summary: The I101T variant, along with C124S, increased soma size more than GFP, suggesting a change in molecular function related to neuronal growth. Evidence Type: Functional | Mutation: G132D | Summary: The G132D variant also increased soma size more than GFP, indicating an alteration in molecular function associated with neuronal growth. Evidence Type: Functional | Mutation: D268E | Summary: The D268E variant appeared wild-type-like in all measures of growth and synaptogenesis, suggesting it does not alter molecular function significantly.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:I101T

Genes: 5728

Variants: A79T C124S D268E G132D I101T

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant did not exhibit a delay in eclosion compared to the empty vector control, indicating a functional alteration in its role in insulin signaling. Evidence Type: Functional | Mutation: G129E | Summary: The G129E variant exhibited eclosion significantly faster than the empty vector control, suggesting a functional change in its activity. Evidence Type: Functional | Mutation: N117S | Summary: The N117S variant slowed the developmental rate further than the wild-type, indicating a functional alteration in its role. Evidence Type: Functional | Mutation: Q298E | Summary: The Q298E variant also slowed the developmental rate further than the wild-type, suggesting a functional change in its activity.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:N117S 5728:Q298E

Genes: 5728

Variants: C124S G129E N117S Q298E

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant is described as catalytically inactive and is involved in genetic interactions that alter PI3P metabolism, indicating a change in molecular function.

Gene→Variant (gene-first): 5728:C124S

Genes: 5728

Variants: C124S

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: C124S | Summary: C124S is characterized as catalytically inactive for both protein and lipid phosphatase functions, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: G129E | Summary: G129E is described as a lipid phosphatase-dead variant, which suggests it alters the biochemical function of the PTEN protein. Evidence Type: Functional | Mutation: Y138L | Summary: Y138L is identified as a protein phosphatase-dead variant, indicating a change in the molecular function of the PTEN protein. Evidence Type: Oncogenic | Mutation: C124S | Summary: C124S has been found in somatic cancer, suggesting it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: R130X | Summary: R130X is associated with somatic cancer, indicating its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: R335X | Summary: R335X is commonly associated with somatic cancer, suggesting it contributes to tumor development or progression.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:R130X 5728:R335X 5728:Y138L

Genes: 5728

Variants: C124S G129E R130X R335X Y138L

[Paper-level Aggregated] PMCID: PMC7190743

Evidence Type(s): Oncogenic, Functional, Predictive, Predisposing

Justification: Oncogenic: The text mentions that certain PTEN variants, including C124S and G129E, have been found in somatic cancer, indicating their potential role in cancer development. Functional: The study assesses the functionality of various PTEN variants through multiple assays, demonstrating that many variants exhibit loss of function (LoF) or gain of function (GoF) phenotypes, impacting cellular processes such as synaptogenesis and insulin signaling. Predictive: The classification of variants as Pathogenic or Likely Pathogenic based on their functional impact suggests that these variants can predict disease outcomes, particularly in relation to ASD and other disorders. Predisposing: The identification of variants associated with ASD, intellectual disability, and developmental delay indicates that these genetic alterations may predispose individuals to these conditions.

Gene→Variant (gene-first): PTEN(5728):A126D PTEN(5728):A126P PTEN(5728):C124S PTEN(5728):G129E PTEN(5728):H123Q PTEN(5728):P354Q PTEN(5728):P38H PTEN(5728):Q396R PTEN(5728):R130L PTEN(5728):R130Q PTEN(5728):A79T PTEN(5728):D268E PTEN(5728):G132D PTEN(5728):I101T PTEN(5728):T167N PTEN(5728):Y176C PTEN(5728):C211W PTEN(5728):E157G PTEN(5728):I135V PTEN(5728):I203V PTEN(5728):I400V PTEN(5728):K342N PTEN(5728):K402N PTEN(5728):L345V PTEN(5728):L70V PTEN(5728):M35V PTEN(5728):N117S PTEN(5728):N228S PTEN(5728):N340D PTEN(5728):N340H PTEN(5728):N356D PTEN(5728):Q298E PTEN(5728):S229T PTEN(5728):T202I PTEN(5728):T78A PTEN(5728):W274L PTEN(5728):Y180H PTEN(5728):Y65C PTEN(5728):R130X PTEN(5728):R335X PTEN(5728):Y138L PTEN(5728):H93Y PTEN(5728):R14G PTEN(5728):R15S

Genes: PTEN(5728)

Variants: A126D A126P C124S G129E H123Q P354Q P38H Q396R R130L R130Q A79T D268E G132D I101T T167N Y176C C211W E157G I135V I203V I400V K342N K402N L345V L70V M35V N117S N228S N340D N340H N356D Q298E S229T T202I T78A W274L Y180H Y65C R130X R335X Y138L H93Y R14G R15S

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 25

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage discusses the classification of variants as Pathogenic and Likely Pathogenic, indicating their association with specific diseases or subtypes, which aligns with the definition of diagnostic evidence.

Gene→Variant (gene-first): 5728:A79T 5728:C211W 5728:E157G 5728:H123Q 5728:I135V 5728:I203V 5728:I400V 5728:K342N 5728:K402N 5728:L345V 5728:L70V 5728:M35V 5728:N117S 5728:N228S 5728:N340D 5728:N340H 5728:N356D 5728:P354Q 5728:Q298E 5728:S229T 5728:T202I 5728:T78A 5728:W274L 5728:Y176C 5728:Y180H 5728:Y65C

Genes: 5728

Variants: A79T C211W E157G H123Q I135V I203V I400V K342N K402N L345V L70V M35V N117S N228S N340D N340H N356D P354Q Q298E S229T T202I T78A W274L Y176C Y180H Y65C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including A126D, A126P, C124S, G129E, H123Q, P354Q, P38H, Q396R, R130L, and R130Q, alter the molecular function of PTEN by affecting pAKT levels, indicating changes in biochemical activity. Oncogenic: The variants are described in the context of their effects on the PI3-AKT signaling pathway and their ability to exhibit loss of function (LoF) or gain of function (GoF), which are indicative of their roles in tumor development or progression.

Gene→Variant (gene-first): 5728:A126D 5728:A126P 5728:C124S 5728:G129E 5728:H123Q 5728:P354Q 5728:P38H 5728:Q396R 5728:R130L 5728:R130Q

Genes: 5728

Variants: A126D A126P C124S G129E H123Q P354Q P38H Q396R R130L R130Q

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants affect protein stability and abundance, indicating that they alter molecular function, which is supported by the use of western blot analysis and flow cytometry to measure these changes.

Gene→Variant (gene-first): 5728:H93Y 5728:P354Q 5728:R130L 5728:R14G 5728:R15S 5728:T78A

Genes: 5728

Variants: H93Y P354Q R130L R14G R15S T78A

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how PTEN variants affect sensorimotor neural circuit function and chemotaxis in C. elegans, indicating that these variants alter molecular or biochemical function. Oncogenic: The context of the passage suggests that the PTEN variants are involved in a pathway related to tumor development or progression, particularly given the focus on mutations in a cancer-related gene.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:P354Q 5728:T167N 5728:Y176C

Genes: 5728

Variants: A79T C124S D268E G132D P354Q T167N Y176C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including C124S, I101T, G132D, D268E, and A79T, alter neuronal growth processes and synapse density, indicating that these variants affect molecular or biochemical functions in neuronal cultures. Oncogenic: The passage mentions that the PHTS variant A79T exhibits a gain-of-function (GoF) phenotype in axonal growth, suggesting that it contributes to tumor development or progression in the context of its association with ASD.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:I101T

Genes: 5728

Variants: A79T C124S D268E G132D I101T

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including C124S, G129E, N117S, and Q298E, alter developmental rates in Drosophila, indicating that these variants affect molecular or biochemical function related to insulin signaling and eclosion timing. Oncogenic: The mention of the known gain-of-function variant 4A inducing lethality suggests that some variants contribute to tumor development or progression, aligning with oncogenic behavior.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:N117S 5728:Q298E

Genes: 5728

Variants: C124S G129E N117S Q298E

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the C124S variant alters molecular interactions and functions within the context of PI3P metabolism and signaling, indicating a change in biochemical activity. Oncogenic: The C124S variant is described in the context of genetic interactions that may contribute to tumor development or progression, as it is involved in a synthetic dosage lethality screen related to PTEN's role in cancer biology.

Gene→Variant (gene-first): 5728:C124S

Genes: 5728

Variants: C124S

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic, Functional

Justification: Diagnostic: The passage discusses the classification of variants, including C124S, G129E, R130X, and R335X, in relation to their association with conditions such as ASD, PHTS, and somatic cancer, indicating their role in defining or confirming these diseases. Oncogenic: The passage mentions that C124S and G129E have been found in somatic cancer, indicating that these variants contribute to tumor development or progression. Functional: The passage describes several variants, including C124S and G129E, as having well-characterized disruptions on protein function, indicating that they alter molecular or biochemical function.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:R130X 5728:R335X 5728:Y138L

Genes: 5728

Variants: C124S G129E R130X R335X Y138L

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 25

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage discusses the classification of variants as Pathogenic and Likely Pathogenic, indicating their association with specific diseases or subtypes, which aligns with the definition of diagnostic evidence.

Gene→Variant (gene-first): 5728:A79T 5728:C211W 5728:E157G 5728:H123Q 5728:I135V 5728:I203V 5728:I400V 5728:K342N 5728:K402N 5728:L345V 5728:L70V 5728:M35V 5728:N117S 5728:N228S 5728:N340D 5728:N340H 5728:N356D 5728:P354Q 5728:Q298E 5728:S229T 5728:T202I 5728:T78A 5728:W274L 5728:Y176C 5728:Y180H 5728:Y65C

Genes: 5728

Variants: A79T C211W E157G H123Q I135V I203V I400V K342N K402N L345V L70V M35V N117S N228S N340D N340H N356D P354Q Q298E S229T T202I T78A W274L Y176C Y180H Y65C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including A126D, A126P, C124S, G129E, H123Q, P354Q, P38H, Q396R, R130L, and R130Q, alter the molecular function of PTEN by affecting pAKT levels, indicating changes in biochemical activity. Oncogenic: The variants are described in the context of their effects on the PI3-AKT signaling pathway and their ability to exhibit loss of function (LoF) or gain of function (GoF), which are indicative of their roles in tumor development or progression.

Gene→Variant (gene-first): 5728:A126D 5728:A126P 5728:C124S 5728:G129E 5728:H123Q 5728:P354Q 5728:P38H 5728:Q396R 5728:R130L 5728:R130Q

Genes: 5728

Variants: A126D A126P C124S G129E H123Q P354Q P38H Q396R R130L R130Q

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants affect protein stability and abundance, indicating that they alter molecular function, which is supported by the use of western blot analysis and flow cytometry to measure these changes.

Gene→Variant (gene-first): 5728:H93Y 5728:P354Q 5728:R130L 5728:R14G 5728:R15S 5728:T78A

Genes: 5728

Variants: H93Y P354Q R130L R14G R15S T78A

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how PTEN variants affect sensorimotor neural circuit function and chemotaxis in C. elegans, indicating that these variants alter molecular or biochemical function. Oncogenic: The context of the passage suggests that the PTEN variants are involved in a pathway related to tumor development or progression, particularly given the focus on mutations in a cancer-related gene.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:P354Q 5728:T167N 5728:Y176C

Genes: 5728

Variants: A79T C124S D268E G132D P354Q T167N Y176C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including C124S, I101T, G132D, D268E, and A79T, alter neuronal growth processes and synapse density, indicating that these variants affect molecular or biochemical functions in neuronal cultures. Oncogenic: The passage mentions that the PHTS variant A79T exhibits a gain-of-function (GoF) phenotype in axonal growth, suggesting that it contributes to tumor development or progression in the context of its association with ASD.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:I101T

Genes: 5728

Variants: A79T C124S D268E G132D I101T

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including C124S, G129E, N117S, and Q298E, alter developmental rates in Drosophila, indicating that these variants affect molecular or biochemical function related to insulin signaling and eclosion timing. Oncogenic: The mention of the known gain-of-function variant 4A inducing lethality suggests that some variants contribute to tumor development or progression, aligning with oncogenic behavior.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:N117S 5728:Q298E

Genes: 5728

Variants: C124S G129E N117S Q298E

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the C124S variant alters molecular interactions and functions within the context of PI3P metabolism and signaling, indicating a change in biochemical activity. Oncogenic: The C124S variant is described in the context of genetic interactions that may contribute to tumor development or progression, as it is involved in a synthetic dosage lethality screen related to PTEN's role in cancer biology.

Gene→Variant (gene-first): 5728:C124S

Genes: 5728

Variants: C124S

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic, Functional

Justification: Diagnostic: The passage discusses the classification of variants, including C124S, G129E, R130X, and R335X, in relation to their association with conditions such as ASD, PHTS, and somatic cancer, indicating their role in defining or confirming these diseases. Oncogenic: The passage mentions that C124S and G129E have been found in somatic cancer, indicating that these variants contribute to tumor development or progression. Functional: The passage describes several variants, including C124S and G129E, as having well-characterized disruptions on protein function, indicating that they alter molecular or biochemical function.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:R130X 5728:R335X 5728:Y138L

Genes: 5728

Variants: C124S G129E R130X R335X Y138L