PatientID: 123

KindredID: 43

Case: M, Age 60Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband (patient 122) had a father who was genetically confirmed with the mutation. The patient's father presented with a CNS hemangioblastoma at 27, renal cell carcinoma at 48, and multiple pancreatic cysts/ tumors at 60.

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0001732; HP:0005584 (Hemangioblastoma, Pancreatic cysts, Abnormality of the pancreas, Renal cell carcinoma)

CaseHPOFreeText: The proband's father (patient 123) presented with a CNS hemangioblastoma at age 27, renal cell carcinoma at age 48, and multiple pancreatic cysts/tumors at age 60.

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.W117R (c.349T>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753664; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.349T%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117R (c.349T>A)

MultipleGeneVariants: N/AcDNAposition:349

PatientID: 253

KindredID: 98

Case: F, 27Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband, patient 253, presented with a CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at age 27. Their father (patient 254) was asymptomatic at the time of assessment. Their grandmother (patient 255) presented with renal cell carcinoma at 60 and multiple pancreatic cysts/tumors at 27, but passed away before diagnosis/ before the mutation could be confirmed.

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0001732; HP:0005584 (Hemangioblastoma, Pancreatic cysts, Abnormality of the pancreas, Renal cell carcinoma)

CaseHPOFreeText: The patient presented with a CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at age 27.

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This cohort was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: Exon 1 Deletion (c.1-?_340+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1 Deletion

MultipleGeneVariants: N/A

PatientID: 37

KindredID: 12

Case: F, 27Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The patient had the same germline mutation as her brother (the proband) and father. Her brother presented with CNS Hemangioblastoma, Renal cell carcinoma, and multiple pancreatic cysts/tumors at the age of 34. Her father presented with renal cell carcinoma at 55. The patient's uncle passed away before diagnosis and presented with a CNS hemangioblastoma at age 19, but could not be genetically confirmed for the mutation.

CasePresentingHPOs: HP:0001737; HP:0001732 (Pancreatic cysts, Abnormality of the pancreas)

CaseHPOFreeText: The patient presented with multiple pancreatic cysts/tumors at the age of 27.

CaseNotHPOs: HP:0010797; HP:0009711; HP:0002666; HP:0005584 (Hemangioblastoma, Retinal capillary hemangioma, Pheochromocytoma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This cohort was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.N78S (c.233A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 93326, https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: N78S (c.233A>G)

MultipleGeneVariants: N/A

PatientID: 291

KindredID: 115

Case: M, 31Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0001732; HP:0001737; HP:0005584; HP:0002666 (Hemangioblastoma, Abnormality of the pancreas, Pancreatic cysts, Renal cell carcinoma, Pheochromocytoma)

CaseHPOFreeText: The proband, patient 291, presented with a CNS hemangioblastoma at 27, and at 31 presented with renal cell carcinoma, multiple pancreatic cysts/tumors, and pheochromocytoma.

CaseNotHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This cohort was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: Exon 3 Deletion (c.464-?_642+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 3 Deletion

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 27Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009713; HP:0000479; HP:0001737 (Spinal hemangioblastoma, renal cysts, pancreatic cysts)

CaseHPOFreeText: The patient, a 27Y male, presented with severe back pain, paraplegia and urinary retention, and numbness below his waist. Upon investigation, a cystic lesion with enhancing nodules expanding the cervical cord from C2 to C3 and an irregular enhancing mass expanding from T6 to T9 associated with extensive edema. Further investigation found multiple cystic lesions scattered throughout the pancreas and both kidneys. The patient’s neurological symptoms resolved after tumour removal.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: T105P(c.313A>C)

LegacyVariant: N/A

ClinVarID: 496055, https://www.ncbi.nlm.nih.gov/clinvar/variation/496055/

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: T105P(c.313A>C)

MultipleGeneVariants: N/A

PatientID: 21

KindredID: 12

Case: F, 27Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated.

CasePresentingHPOs: HP:0002893; HP:0002666 (Pituitary adenoma, Pheochromocytoma)

CaseHPOFreeText: Pituitary adenoma presented at age 27. Pheochromocytoma age of presentation unknown.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: MAX/RET/TMEM127/SDHA/SDHB/SDHC/SDHD/SDHAF2

PreviouslyPublished: N/A

SupplementalData: Table 1, Supplementary Table 6

Variant: p.D197N (c.589G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756524, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA351756524

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: D197N (c.589G>A)

MultipleGeneVariants: Germline, SDHA, c.91C>T (p.Arg31*)

PatientID: P1

KindredID: P1

Case: F, 27Y0M, Ethnicity Unknown

DiseaseAssertion: Paraganglioma

FamilyInfo: N/A

CohortInfo: Tumour samples and paired peripheral blood samples were obtained from 39 patients, consisting of 31 PCs, seven extra adrenal PGLs and one metastasis from a malignant PC previously presenting with a PC.

CasePresentingHPOs: HP:0002668 (paraganglioma)

CaseHPOFreeText: The patient had a malignant extraadrenal paraganglioma measuring 13 mm at age 27.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET/SDHB/SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T157I (c.470C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: T157I (c.470C>T)

MultipleGeneVariants: N/A

PatientID: 8

KindredID: 8

Case: M, 27Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Positive family history for VHL.

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0009711; HP:0005584; HP:0002668; HP:0001737; HP:0002666 (retinal capillary hemangioma, renal cell carcinoma, paraganglioma, pancreatic cysts, pheochromocytoma)

CaseHPOFreeText: At 19Y (in 1997), he presented with headaches, ophthalmological examination showed a right retinal hemangioblastoma (treated by laser). 5 years later (age 24Y) he had a right nephrectomy and left nephron-sparing surgery for renal cell carcinoma. Age 27, a palpable mass on the left side of the neck. CT and MRI revealed a 4-cm carotid body tumor (paraganglioma). The patient also has pancreatic cysts. 

CaseNotHPOs: HP:0010797 (hemangioblastoma)

CaseNotHPOFreeText: MRI scan from case presenting headaches showed a normal CNS

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: exon 2-3 deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: EXON 2-3 DELETION

MultipleGeneVariants: N/A

PatientID: None

KindredID: F (proband)

Case: M, 27Y0M, Hungarian

DiseaseAssertion: VHL

FamilyInfo: His mother was also found to have this mutation and she had renal cell carcinoma at age 49.

CasePresentingHPOs: HP:0009711, HP:0002666, HP:0000085 (retinal capillary hemangioma, pheochromocytoma, Horseshoe kidney)

CaseHPOFreeText: Patient developed retinal hemangiomas and unilateral pheochromocytoma at the age of 27 years. Abdominal CT showed also horseshoe kidneys.

CaseNotHPOs: HP:0010797, HP:0005584 (hemangioblastoma, renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: N/A

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence:N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500 G >A)

MultipleGeneVariants: N/A

GroupID: 35

DiseaseAssertion: assumed VHL

GroupSize: 10

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 10 of the 573 patients discussed in this paper were found to have the following mutation belonging to 2 families altogether.

GroupPresentingHPOs: HP:0006880; HP:0009711; HP:0005584; HP:0002666 (cerebellar hemangioblastoma, retinal capillary hemangioma; renal cell carcinoma; pheochromocytoma)

GroupHPOFreeText: 8 patients had retinal angiomas diagnosed at a mean age of 27Y, 4 had cerebellar hemangioblastomas diagnosed at a mean age of 31Y, 1 member had RCC diagnosed at 50Y, and one has pheochromocytoma diagnosed at 27Y.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.R177* (c.529A>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 625258 https://www.ncbi.nlm.nih.gov/clinvar/variation/625258/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: R177* (c.529A>T)

MultipleGeneVariants: N/A

PatientID: 156

KindredID: 58

Case: F, 27Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband (patient 155) has a sister (patient 156) and a nephew (son of sister, patient 157) that were both genetically confirmed with the mutation. The sister presented with a CNS hemangioblastoma at 21 and multiple pancreatic cysts/tumors at 27, and the nephew was asymptomatic at the time of analysis.

CasePresentingHPOs: HP:0001737; HP:0001732; HP:0010797 (Pancreatic cysts, Abnormality of the pancreas, Hemangioblastoma)

CaseHPOFreeText: The proband's sister presented with a CNS hemangioblastoma at 21, and multiple pancreatic cysts/tumors at 27.

CaseNotHPOs: HP:0002666; HP:0005584; HP:0009711 (Pheochromocytoma, Renal cell carcinoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.E160Dfs*10 (c.480del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432423139; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA432423139

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: E160fs (c.480delG)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: F, 38Y0M, German

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo:All patients from the German registry for VHL with PNETs >3 cm diameter with tumours located in the pancreatic body or tail region.

CasePresentingHPOs: HP:0009711, HP:0009713, HP:0006880, HP:0009726, HP:0030405, HP:0001737 (retinal capillary hemangioma, spinal hemangioblastoma, cerebellar hemangioblastoma, renal neoplasm, pancreatic endocrine tumour, pancreatic cysts)

CaseHPOFreeText: Retinal angiomatosis at age 17, hemangioblastoma of the cervical spinal cord at age 24, cerebellar hemangioblastoma at age 27, left renal tumor at age 36. Pancreatic endocrine tumour and pancreatic cysts at age 38. She had a laparoscopy which found an 8-cm retrogastric cyst, 3.2-cm benign PNET, and a serous cystadenoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q132* (c.394C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 288749 https://www.ncbi.nlm.nih.gov/clinvar/variation/288749/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: Q132* (c.394C>T)

MultipleGeneVariants: N/A

PatientID: 9

KindredID: 5

Case: F, 46Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: A family pedigree is provided in figure 1. Neither parent had VHL syndrome characterized by retinal capillary hemangiomas (RCHs). They likely did not undergo molecular testing because there was no mention of de novo status.

CasePresentingHPOs: HP:0006880; HP:0009711; HP:0009713; HP:0000541 (Cerebellar hemangioblastoma; Retinal capillary hemangioma; Spinal hemangioblastoma; Retinal detachment)

CaseHPOFreeText: A 32-year-old woman had been diagnosed in 2000 with multiple cerebellar and spinal hemangioblastomas. In 2005, she was examined at the eye clinic and were visual acuity was 20/20 and 20/25 in the right and left eye, respectively. No abnormalities were found in the right eye, but a peripheral RCH that was already partially treated with laser was observed in the left eye. Many tiny RCHs that surrounded the major lesion were also detected in this eye. Further laser treatments were scheduled, but the patient did not follow-up and instead came to the ophthalmic emergency service three years later. Visual acuity of the left eye worsened to 20/640, and she presented with retinal detachment. The partially treated RCH of the left eye worsened and and more tiny RCHs were detected. Cryotherapy was performed in the left eye but retinal detachment was still present at follow up. On follow up, no RCHs were detected in the right eye and vision loss developed in both eyes.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Patient did not have other known tumours.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R113* (c.337C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 220414, https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: R113* (c.337C>T)

MultipleGeneVariants: N/A

PatientID: 1 (Proband)

KindredID: 12

Case: M, 57Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: This patient had a father that was assumed to have the c.406T>C germline mutation of the VHL gene but was not confirmed genetically. His father presented with renal cell carcinoma and died at 47Y.

CasePresentingHPOs: HP:0010797; HP:0009711; HP:0000077; HP:0001732 (Hemangioblastoma, Retinal capillary hemangioma, Abnormality of the kidney, Abnormality of the pancreas)

CaseHPOFreeText: This patient presented with CNS hemangioblastoma (37Y), retinal angioma (27Y) and renal and pancreatic cyst or tumor (unspecified) (28Y).

CaseNotHPOs: HP:0002666; HP:0005584 (Pheochromocytoma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

Variant: p.S65P (c.193T>C)

LegacyVariant: c.406T>C

CaseProblemVariantFreeText: N/A

ClinVarID: 547829, https://www.ncbi.nlm.nih.gov/clinvar/variation/547829/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variant reference sequence is unclear in the current paper. After consulting the SickKids patient database, and finding the protein change to be recorded as: p.Ser65Pro, it was concluded that the current paper reported the cDNA change according to the legacy reference sequence (AF010238.1) and was mapped to c.193T>C (NM_000551.3).

MutationType: missense_variant;transition

CivicName: S65P (c.193T>C)

MultipleGeneVariants: N/A

PatientID: Mother

KindredID: 12

Case: F, 48Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: Daughter presented with the same variant and pheochromocytoma at 24Y, multiple pancreatic lesions (pancreatic cyst or tumor, unspecified) at 21Y.

CohortInfo: Thirteen unrelated patients with germline VHL mutations who were diagnosed with VHL disease were evaluated.

CasePresentingHPOs: HP:0001732; HP:0002666 (Abnormality of the pancreas, Pheochromocytoma)

CaseHPOFreeText: Pheochromocytoma at 27Y, multiple pancreatic lesions (pancreatic cyst or tumor, unspecified) at 48Y a developmental venous anomaly or meningioma (unspecified). Diagnosed with VHL Type 2C.

CaseNotHPOs: HP:0010797; HP:0005584; HP:0009711; HP:0000107 (Hemangioblastoma, Renal cell carcinoma, Retinal capillary hemangioma, Renal cyst)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L198Wfs*4 (c.592del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432423813, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.592del

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion; minus_1_frameshift_variant

CivicName: L198fs (c.592del)

MultipleGeneVariants: N/A

GroupID: 10

DiseaseAssertion: assumed VHL

GroupSize: 6

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Chinese

GroupAgeRange: 47.0Y +/- 18.4Y

GroupInfo: Clinical characteristics of 258 patients from 80 unrelated Chinese families were reported in this study. Grouped by the 21 mutations found, 2 families with 6 members total were described, and phenotypic information was given for this group.

GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0005584; HP:0001737; HP:0009715 (hemangioblastoma, retinal capillary hemangioma, renal cell carcinoma, pancreatic cysts, papillary cystadenoma of the epididymis)

GroupHPOFreeText: 3 of the 6 members presented with CNS hemangioblastoma (mean age of 40.0Y), 3/6 had retinal capillary hemangiomas (at a mean age of 23Y), renal cell carcinoma in 3 members (at a mean age of 35.3Y), pancreatic cysts in 2 members (with age of onsets of 26 and 27Y), and 1 with a papillary cystadenoma of the epididymis genital system tumor (epididymis or broad ligament) (at age 18Y).

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: no members were found with pheochromocytomas

GroupPreviousTesting: N/A

PreviouslyPublished: 29330336

SupplementalData: N/A

Variant: p.R113* (c.337C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: R113* (c.337C>T)

MultipleGeneVariants: N/A

GroupID: 85

Case: 27Y0M, Sex Unknown, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: 1 of the 573 patients discussed in this paper were found to have this variant. This mutation (c.538A>G) was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

CaseHPOFreeText: patient had RCCs diagnosed at 27Y

CaseNotHPOs: HP:0009711; HP:0006880; HP:0002666 (retinal capillary hemangioma; cerebellar hemangioblastoma; pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.I180V (c.538A>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 161401 https://www.ncbi.nlm.nih.gov/clinvar/variation/161401/

CAID: N/A

gnomAD: 0.00001061 https://gnomad.broadinstitute.org/variant/3-10191545-A-G

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: I180V (c.538A>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: B

Case: M, 27Y0M, Hungarian

DiseaseAssertion: VHL

FamilyInfo: The parents of the patient rejected clinical and genetic screening, whereas clinical screening in a younger brother of the index patient revealed no abnormality.

CasePresentingHPOs: HP:0009711, HP:0000107, HP:0001737, HP:0001901, HP:0006880 (retinal capillary hemangioma, renal cyst, pancreatic cysts, polycythemia, cerebellar hemangioblastoma)

CaseHPOFreeText: Retina involvement presented at age 19. The patient had cerebellar hemangioma as well as renal and pancreatic cysts at the age of 27 years.

CaseNotHPOs: HP:0005584, HP:0002666 (renal cell carcinoma, pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R161* (c.481C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: R161* (c.481C>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: F, 33Y0M, Japanese

DiseaseAssertion: VHL

FamilyInfo: Her father and elder brother were also diagnosed with VHLD, with her father having a medical history of two surgical resections for pancreatic NET and associated metastatic recurrence in the liver.

CasePresentingHPOs: HP:0030405, HP:0009713, HP:0005584, HP:0010797 (Pancreatic endocrine tumor, Spinal hemangioblastoma, Renal cell carcinoma, hemangioblastoma)

CaseHPOFreeText: She first developed multiple solid tumors of the pancreas at age 27 and they continued to grow until she was referred to the institute at age 33. She had a pancreatic endocrine tumour at age 14. At age 19, she had hemangiomas of the fourth ventricle and cervical spinal cord and a renal cell carcinoma of the right kidney treated by nephrectomy at 30 years of age.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: N/A

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence: Immunohistochemical studies revealed that the tumor cells were positive for synaptophysin and chromogranin A.

MutationType: missense_variant;transition

CivicName: R167Q (c.500G>A)

MultipleGeneVariants: N/A

PatientID: 36

KindredID: 6015

Case: F, 27Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

CaseHPOFreeText: She presented with three pathologic pancreatic endocrine tumours.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167W (c.499C>T)

LegacyVariant: p.R167W (c.712C>T)

CaseProblemVariantFreeText: N/A

ClinVar: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

CAID: CA020450 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.499C%3ET

gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: 11

Case: F, 36Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: There was said to be, at the time, no affected relatives

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0006748; HP:0002668; HP:0006476; HP:0006880; HP:0009711; HP:0000618; HP:0010797 (adrenal pheochorocytoma, paraganglioma, abnormality of the pancreatic islet cells, cerebellar hemangioblastoma, retinal capillary hemangioblastoma, blindness, hemangioblastoma)

CaseHPOFreeText: At 8Y, (in 1978), she was operated for a right pheochromocytoma; at age 13 for a contralateral pheochromocytoma; at age 15, for a 4-cm mass at the neck was diagnosed by selective arteriography as a carotid paraganglioma. The patient was then operated twice for cerebellar hemangioblastoma at age 22, leading to the diagnosis of VHL disease. At age 27, the patient was operated again for a retrocaval pheochromocytoma and for islet cell tumors. The patient was also repeatedly treated for bilateral retinal hemangioblastomas leading to blindness at age 32. At age 36, again a pheochromocytoma was removed

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T157I (c.470C>T)

LegacyVariant: p.T157I

CaseProblemVariantFreeText: The publication only provides the p., the mutation was able to be deduced to p.T157I (c.470C>T)

ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: T157I (c.470C>T)

MultipleGeneVariants: N/A

PatientID: 184

KindredID: 71

Case: M, Age 27Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband's mother (patient 185) was confirmed with the mutation but was asymptomatic at the time of testing. The proband (patient 184) presented with renal cell carcinoma at 27, and multiple pancreatic cysts/tumors and a pheochromocytoma at age 24.

CasePresentingHPOs: HP:0005584, HP:0002666, HP:0001737, HP:0001732 (Renal cell carcinoma, Pheochromocytoma, Pancreatic cysts, Abnormality of the pancreas)

CaseHPOFreeText: The proband presented with renal cell carcinoma at 27, and multiple pancreatic cysts/tumors and a pheochromocytoma at age 24.

CaseNotHPOs: HP:0010797; HP:0009711 (Hemangioblastoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in an earlier paper by Wang et al., 2014 (PMID 24581539) as well as a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.R167W (c.499C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2218; https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

CAID: N/A

gnomAD: 0.000007954; https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

I think this definition shows that the American Dream is not only about financial success, but also about having a meaningful and fulfilling life. However, the emphasis on individual ability and achievement raises an important question: does everyone have a fair chance to succeed? Even if people work equally hard, their opportunities may differ because of their circumstances.

Does having more money make it easier for people to achieve the American Dream? Why? This difference suggests that money can affect how people view their chances of success. George and Lennie are poor migrant workers who struggle to save enough money to buy land. This connects to the novel because their dream depends not only on hard work but also on having enough money and opportunities.

endovascular stenting emerging as first-line therapy for rapid symptom relief, while definitive treatment targets the underlying cause

Google users are less likely to click on links when an AI summary appears in the results by [[Athena Chapekis]] and [[Anna Lieb]]

Gutting Book Basics by [[Thomas Vander Wal]]

Die Tat interview die Politologin Sonja Tiges zur Antikrimapolitik der Trampadministration in ihren ersten 100 Tagen. Tielges betont unter anderem, dass die Trumpregierung eine Energiedominanz anstrebt und andere Länder dazu drängt, das fossile Modell beizubehalten. Möglicherweise strebe China eine Gegenposition an, unter anderem verändere sich die Bereitschaft klimafinanzend zur Verfügung zu stellen in China.

https://taz.de/Wissenschaftlerin-zur-US-Klimapolitik/!6081981/

In Frankreich droht das rechtsradikale Rasmula-Morne-National damit die Regierung bei Ruhen zu stürzen, wenn die neue, mehrjährige Energieplanung per Decret durchgesetzt wird. Man wird sich insbesondere gegen die Finanzierung des Netzausbaus für erneuerbare Energien geben. Die Rechtspopulisten präsentieren sich als Fakträther niedriger Energiepreise und des Ausbaus der Kernenergie. https://www.liberation.fr/politique/elections/energie-pourquoi-le-rn-menace-de-censurer-le-gouvernement-sur-la-feuille-de-route-francaise-20250427_D22IUWR2ABE7TKGZSFKYVEC3EI/

Washington Post-Artikel (mit Links zur Quelle) zu den Forschungen von Ki-Wen Seo und anderen zu den Veränderungen im globalen Wasserkreislauf durch die Erderhitzung. Für den Anstieg des Meeresspiegels war die Austrocknung großer Gebiete auf dem Festland wenigstens in einigen Jahren wichtiger als das Schmelzen des grönländischen Eisschilds. Mit hoher Wahrscheinlichkeit handelt es sich bei dem Wasserverlust um ein irreversibles Phänomen. Es zwingt zu dauerhaften Veränderungen in der Landwirtschaft https://www.washingtonpost.com/climate-environment/2025/03/27/earth-soil-moisture-drying-sea-level-study/

https://phys.org/news/2025-03-earth-storage-soil-lakes-rivers.html

https://www.theguardian.com/world/2025/mar/27/south-korea-fires-death-toll-rises-worst-in-history

https://www.derstandard.at/story/3000000262919/staatssekretaerin-zehetner-kommunikation-zu-erneuerbaren-war-unehrlich

’Tis true; then learn how false, fears be:

In line 27, the speaker agrees how there is no consequence and seems to fear something, but, that something is unknown.

https://www.derstandard.at/story/3000000259256/steirisches-kulturkuratorium-wurde-in-hauruckaktion-von-fpoe-umgebaut

https://www.kleinezeitung.at/kultur/stmk_kultur/19410066/zum-umbau-des-kulturkuratoriums-vereinnahmte-ahnungslose-parteisoldaten

https://www.kleinezeitung.at/kultur/stmk_kultur/19407717/so-sieht-das-neue-kulturkuratorium-der-steiermark-aus

650 Angestellte der US-Klima- und Wetterbehörde NOAA haben in dieser Woche Kündigungsschreiben erhalten, das sind etwa 5% des Personals. Die Behörde soll sich sich offenbar auf die Wettervorhersage konzentrieren, während u.a. Klimawissenschaftler:innen Ziel einer Säuberung sind. Das Great Lakes Environmental Research Laboratory der NOAA stellt seine Öffentlichkeitsarbeit wegen Personalkürzungen ein. Durch den Personalabbau, auf den NGOs und viele Wissenschaftler:innen mit Entsetzen reagierten, werden Services unmöglich, die u.a. für Landwirtschaft, Fischerei und Meeresschutz essentiell sind. Die Abwicklung der NOAA gehört zu den im „Project 2025“ vorgesehenen Maßnahmen. https://www.latimes.com/california/story/2025-02-27/mass-firings-noaa-national-weather-service-ignite-fury

https://www.derstandard.at/story/3000000254677/hitzebedingte-todesfaelle-nehmen-in-den-naechsten-jahrzehnten-deutlich-zu

for - adjacency - progress trap - mafia - intentional fires - Italy - complexity - CNN - How the Mafia is weaponizing wildfires - 2025,Jan 27

Der britische Premierminister Richi Sunak hat das Ok für die Ausbeutung des Rosebank Field gegeben, des größten noch nicht genutzten britischen Öl- und Gsvorkommens in der Nordsee. In der ersten Phase sollen ab 2026/27 245 Millionen Barrel Öl sowie Gas gefördert werden. Eiine Woche zuvor wurde die Verschärfung der Umweltstandards für Heizungen und Autos in Großbritannien aufgeschoben.

https://www.liberation.fr/environnement/le-royaume-uni-ouvre-la-porte-a-lexploitation-dun-nouveau-champ-de-petrole-20230927_56LVXX7RSNH2FOVT74OEXZ5H3I/?redirected=1

Ein von 1000 Wissenschaftler:innen unterzeichnetes Papier, das sich für den Konsum vom Fleisch ausspricht, ist das Ergebnis einer PR- und Lobbying-Aktion der Fleischindustrie. Es diente der Beeinflussung der EU-Kommission. Der EU-Agrarkommissar übernahm die Argumentation. Offenbar ist es mit Hilfe der sogenannten Dublin Declaration, die von Fachleuten als wenig qualitätvoll beurteilt wird, gelungen, die EU-Kommission von ihrer ursprünglichen Absicht, Einschränkungen bei der Fleisch- und Milchproduktion zu vertreten, abzubringen. https://www.theguardian.com/environment/2023/oct/27/revealed-industry-figures-declaration-scientists-backing-meat-eating

for - Eduardo do Silveira Campos homepage - IFEN - Institute of Phenomenological-existential psychology - from - article - Medium - The truth of San Vicente in the voice of Milton Nascimento Mosaic Institute - Eduardo Campos - 2017, Oct 27 - https://hyp.is/V6DIJMuaEe-hQ1OPLsWsTw/medium.com/instituto-mosaico/a-verdade-de-san-vicente-na-voz-de-milton-nascimento-3ca69d241c53

for - article - Medium - The truth of San Vicente in the voice of Milton Nascimento Mosaic Institute - Eduardo Campos - 2017, Oct 27 - from - music - review Milton Nascimento. Lo Borges - Clube Da Esquina - Classic Music Review - San Vicente - altrochchick - 2021, April 11 - https://hyp.is/krcU1suaEe-s5zcLEaXR3Q/altrockchick.com/2021/04/11/milton-nascimiento-lo-borges-clube-da-esquina-classic-music-review/ - from - youtube - music - San Vicente - Milton Nascimento - Live at Montreal Jazz Festival - moving performance - https://hyp.is/oElbPsucEe-nqit3PkZ2Bg/www.youtube.com/watch?v=H0BLHm7uyO0 - Investigate possibility - Deep Humanity BEing journey - San Vicente - Milton Nascimento

for - music - review Milton Nascimento. Lo Borges - Clube Da Esquina - Classic Music Review - San Vicente - altrochchick - 2021, April 11 - to article - Medium - The truth of San Vicente in the voice of Milton Nascimento Mosaic Institute - Eduardo Campos - 2017, Oct 27 - https://hyp.is/V6DIJMuaEe-hQ1OPLsWsTw/medium.com/instituto-mosaico/a-verdade-de-san-vicente-na-voz-de-milton-nascimento-3ca69d241c53 - from - youtube - music - San Vicente - Milton Nascimento - Live at Montreal Jazz Festival - moving performance - https://hyp.is/oElbPsucEe-nqit3PkZ2Bg/www.youtube.com/watch?v=H0BLHm7uyO0

for - stats - 27% of the gap can be reduced by wind and solar deployment and 20% by action on forests, while efficiency, electrification, fuel switching in buildings, transport and industry sectors can also contribute - UN Emissions Gap Report 2024 - Key Messages

https://www.theguardian.com/world/2024/nov/27/von-der-leyen-more-eu-defence-spending-russia-european-commission-election

Find out more! What was the Russian-American Company? Did they trade things besides sea otter fur?

Cite your source(s)!

1:27:32 A Community Bill of Rights

https://www.repubblica.it/green-and-blue/2024/02/27/news/ue_stretta_sullecocidio_reati_ambientali_europa-422214673/

Aliens in the plot "hide between saccades".

We can equate this to the way politicians actively treat their constituents when they play the hypocratic game of "do as I say not as I do".

https://en.wikipedia.org/wiki/Blindsight_(Watts_novel)

https://danallosso.substack.com/p/science-of-reading-meeting-2

Referenced by Tim

https://www.youtube.com/watch?v=SQAidyYqfnI

https://www.youtube.com/watch?v=uf8zQmqe97g

https://psycnet.apa.org/record/1926-01653-001

https://godandcountrythemovie.com/

They Live (1988)<br /> https://www.imdb.com/title/tt0096256/

https://www.linkedin.com/in/kazukinakayashiki/

https://en.wikipedia.org/wiki/Nixtamalization

In Südfrankreich sind große Teile der Weinernte bereits jetzt verloren. Ursache dafür sind Frosteinbrüche nach extrem hohen Temperaturen. Viele französische Weinbaubetriebe werden voraussichtlich von Versicherungen entschädigt werden.

In Frankreich ist ein Komitee zur Anticipation von Trockenheiten im Ministerium für die ökologische transition zusammengekommen. Der zuständige Minister hat dabei die Situation im Departement Pyrénées Orientales als Vorzeichen dessen bezeichnet, was im ganzen Mittelmeerraum bevorsteht. Er Versuche, einen "Krieg um das Wasser" zu verhindern.https://www.liberation.fr/environnement/climat/secheresse-en-france-le-chaud-dans-linconnu-20230427_75BMFEACMNABDKKZZM7GWCRHAM/

Das Highjacking des UN-Klimaprozesses durch die Fossilindustrien betreiben die Vereinigten Arabischen Emirate in sehr konkreter Weise. Kurz vor der COP28 wurden Notizen zur Vorbereitung von Gesprächen der Emirate mit 27 Staaten bekannt: Bei Klimatreffen sollten gemeinsame Projekte mit der Adnoc zur Öl- und Gasförderung und mit Masdar im Bereich der Erneuerbaren angesprochen werden sollten. Adnoc und Masdar werden von Sultan Al Jaber geleitet, dem Präsidenten der COP28 https://www.theguardian.com/environment/2023/nov/27/cop28-host-uae-planned-promote-oil-deals-climate-talks

Left Behind by [[Nancy Isenberg]]

This is of interest because Isenberg's White Trash came out in January 2016 just a five months before Vance's Hillbilly Elegy was released. As a result she didn't get to reference it in her book.

https://en.wikipedia.org/wiki/C._J._Sansom

https://research.ibm.com/blog/retrieval-augmented-generation-RAG

PK indicates that folks using footnotes in AI are using rag methods.

http://meetingwords.com/RCC30invitation

https://www.cassidyai.com/

Build AI Automations & Assistants Trained on Your Business.

https://www.theguardian.com/environment/2024/mar/27/extreme-heat-summit-to-urge-leaders-to-act-on-threat-from-rising-temperatures

Das Tempo der Temperaturerhöhung an der Oberfläche der Ozeane ist auch für erfahrene Forschende schockierend. Besonders hoch ist es im Nordatlantik, dessen Erwärmung zu schwereren Hurricans führen könnte. Aber auch der Südatlantik und damit das antarktische Meereis sind betroffen. Die Ursachen sind nicht geklärt; das El Niño-Phänomen reicht zur Erklärung nicht aus. Es könnten Feedback-Mechanismen eine Rolle spielen. Die New York Times hat mehrere Wissenschaftler befragt.

https://www.nytimes.com/2024/02/27/climate/scientists-are-freaking-out-about-ocean-temperatures.html

Infografik: https://static01.nyt.com/images/2024/02/07/multimedia/27cli-newsletter-02/2024-02-07-sst-hottest-january-index-superJumbo-v2.png?quality=75&auto=webp

I don't know why she don't want her students use AI.

I think it is an efficiently way cause this is how my teacher taught me to search information with it.

I am surprised that there is a class about the law of AI.

Ghana ist weltweit das Land mit der schnellsten Entwaldungsrate. Die meisten Abholzungen sind illegal und widersprechen der neuen EU-Verordnung zu entwaldungsfreien Lieferketten. Die Bestimmungen werden in großen Stil umgegangen, dabei spielt Korruption eine große Rolle, aber auch mangelnde Kontrolle bei den Importeuren. Reportage der taz. https://taz.de/Abholzung-in-Ghana/!5985427/

Nach der Invasion der ganzen Ukraine durch Russland wurde russisches Gas in Europa vor allem durch LNG-Importe aus den USA ersetzt. Damit tauscht man eine Abhängigkeit durch eine andere ein, statt die Erneuerbaren entschiedener auszubauen. Ausführlicher Bericht von Bloomberg über die damit verbundenen Risiken. Als erstes Zeichen für Schwierigkeiten wird die Verzögerung der Genehmigung von CP2 gewertet. https://www.energyconnects.com/news/gas-lng/2024/january/gas-addicted-europe-trades-one-energy-risk-for-another/

https://www.theguardian.com/environment/2023/dec/27/2023-costliest-climate-disasters-poor-lose-out-global-postcode-lottery

https://www.nytimes.com/2023/04/27/climate/horn-of-africa-somalia-drought.html

Studie: https://www.worldweatherattribution.org/human-induced-climate-change-increased-drought-severity-in-southern-horn-of-africa/

https://www.rnd.de/wissen/hochwasser-in-deutschland-ueber-weihnachten-ist-das-das-neue-normal-im-klimawandel-FPBMNJ2MBJCXZAPN5DSTAFMAOY.html

https://www.derstandard.de/story/3000000201089/klimaerwaermung-heizt-religioes-wirtschaftlichen-konflikt-in-nigeria-an