PatientID: II:1

KindredID: 1

Case: M, 37Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: the patient’s father was observed to be affected with CNS hemangioblastoma at 50Y

CasePresentingHPOs: HP:0010797; HP:0009711; HP:0009715 (hemangioblastoma; retinal capillary hemangioma, Papillary cystadenoma of the epididymis)

CaseHPOFreeText: patient had hemangioblastomas diagnosed at 37Y, retinal capillary hemangioma at 31Y, and epididymal/ovarian cystadenoma at 16Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: exon 2,3 deletion

CaseProblemVariantFreeText: N/A

LegacyVariant: 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: 2

KindredID: 2

Case: F, 31Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient’s father was case 1, who possessed the same mutation and had VHL syndrome. Patient's father died at age 54Y0M.

CasePresentingHPOs: HP:0000107; HP:0001737 (Renal cyst; Pancreatic cysts)

CaseHPOFreeText: The patient was diagnosed as “seronegative arthritis” due to sympathetic polyarticular pain of the extremities at age 12Y0M. At 29Y0M,  she was diagnosed with ankylosing spondylitis. In 2018, CT scan revealed renal and pancreatic cysts. Diagnosed with VHL disease due to symptoms and family history.

CaseNotHPOs: HP:0006880 (Cerebellar hemangioblastoma)

CaseNotHPOFreeText: Patient did not have any brain abnormalities at the time of her CT scan.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R177Tfs*23(c.530_536del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 694389, https://www.ncbi.nlm.nih.gov/clinvar/variation/694389/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: R177Tfs*23(c.530_536del)

MultipleGeneVariants: N/A

PatientID: 23

KindredID: 7

Case: M, 31Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband, patient 23, had a brother (patient 24) and father (patient 25) who were both genetically confirmed with the mutation. The brother presented with a CNS hemangioblastoma, renal cell carcinoma, and pancreatic cysts/tumors at age 32. The father presented with renal cell carcinoma and pancreatic cysts/tumors at age 58.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: The proband, patient 23, presented with a CNS hemangioblastoma at age 31.

CaseNotHPOs: HP:0001737; HP:0001732; HP:0002666; HP:0005584; HP:0009711 (Pancreatic cysts, Abnormality of the pancreas, Pheochromocytoma, Renal cell carcinoma, 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: p.R69Afs*63 (c.204_205insG)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA913189244; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.204_205insG

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: R69AFS*63 (c.204_205insG)

MultipleGeneVariants: N/A

PatientID: 131

KindredID: 49

Case: F, Age 31Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: The proband presented with a pheochromocytoma at 18, retinal angioma at 29, and renal cell carcinoma and multiple pancreatic cysts/tumors at 31.

CaseNotHPOs: HP:0010797 (Hemangioblastoma)

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.F136C (c.407T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 496065; https://www.ncbi.nlm.nih.gov/clinvar/variation/496065/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: F136C (c.407T>G)

MultipleGeneVariants: N/A

PatientID: 9

KindredID: C

Case: Sex Unknown, 35Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Positive VHL family history.

CohortInfo: 10 VHL patients with renal cell carcinoma and a definite VHL family history.

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

CaseHPOFreeText: The patient had a hemangioblastoma diagnosed at age 29. The patient was diagnosed with renal cell carcinoma at age 31. A nephron-sparing surgery was performed on the left side. He was found to have one lesion with a diameter of 2 cm.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 1-2 loss (c.1-?_463+?del)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVar: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1-2 Deletion

MultipleGeneVariants: N/A

PatientID: VHL_6 (tumor ID)

KindredID: 6

Case: F, 31Y0M, Ethnicity Unknown

DiseaseAssertion: Adrenal pheochromocytoma

FamilyInfo: N/A

CasePresentingHPOs: HP:0006748 (Adrenal pheochromocytoma)

CaseHPOFreeText: The patient had a benign adrenal pheochromocytoma at 31Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q164R (c.491A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2238, https://www.ncbi.nlm.nih.gov/clinvar/variation/2238/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: Q164R (c.491A>G)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 6

Case: F, 40Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: Thirteen patients with a supratentorial hemangioblastoma.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: The patient had a hemangioblastoma localized to the corpus callosum at age 31. After surgery the patient was alive with disease. The patient was followed up 108 months later.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 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 3 Deletion

MultipleGeneVariants: N/A

PatientID: 10 (Uncle)

KindredID: 7

Case: M, 36Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 6 members of this family were found to harbor the c.319C>G germline variant of the VHL gene. ID 11 presented with renal and pancreatic abnormalities, pheochromocytoma and other undefined phenotypes. ID 1 presented with pheochromocytoma. ID 2 presented with pancreatic abnormalities. ID 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 4 presented with pheochromocytoma.

CasePresentingHPOs: HP:0002666; HP:0001732; HP:0010797 (Pheochromocytoma, Abnormality of the pancreas, Hemangioblastoma)

CaseHPOFreeText: The patient presented with CNS hemangioblastoma (31Y, 35Y), pancreatic abnormalities (31Y) and pheochromocytoma (13Y).

CaseNotHPOs: HP:0009711; HP:0005584; HP:0000077 (Retinal capillary hemangioma, Renal cell carcinoma, Abnormality of the kidney)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

Variant: p.R107G (c.319C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43599, https://www.ncbi.nlm.nih.gov/clinvar/variation/43599/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R107G (c.319C>G)

MultipleGeneVariants: N/A

PatientID: IV-23

KindredID: 1

Case: M, 35Y0M, Iranian

DiseaseAssertion: assumed VHL

FamilyInfo: Familial history was positive. See Fig 1. A total of 43 members of the kindred, 24 males and 19 females, aged 2-77 years were reached for evaluation. It is stated in the paper that all affected subjects (13) were positive for the same mutation (c.500G>A). Additionally, gene sequencing revealed that 4 asymptomatic members of the kindred also harbored the pathogenic mutation. Phenotypes include pheochromocytoma, hemangioblastoma, and retinal HB.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Patient had a bilateral PCC at 31Y which was surgically removed at the time. He presently has no abnormal findings.

CaseNotHPOs: HP:0000077 (abnormality of the kidney)

CaseNotHPOFreeText: There was no case of kidney tumors among the kindred.

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: N/A

MutationType: missense_variant; transition

CivicName: R167Q (c.500G>A)

MultipleGeneVariants: N/A

PatientID: 8

KindredID: 8

Case: Sex Unknown, 31Y0M, Italian

DiseaseAssertion: pheochromocytoma

FamilyInfo: Present - potential pathogenic relevance due to a family history, although no further information present

CasePresentingHPOs: HP:0006748 (Adrenal pheochromocytoma)

CaseHPOFreeText: adrenal bilateral pheochromocytoma with an age of diagnosis of 31Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93C (c.277G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223175 https://www.ncbi.nlm.nih.gov/clinvar/variation/223175/

CAID: N/A

gnomAD: 0.000004476 https://gnomad.broadinstitute.org/variant/3-10183808-G-T

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G93C (c.277G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: VHL25

Case: M, 31Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: A total of 190 patients recruited by the COMETE network over 15 years were included in the study.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: The patient had one benign pheochromocytoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET/SDHB/SDHC/SDHD

PreviouslyPublished: N/A

SupplementalData: Table 1 of Supplementary

Variant: Complete Deletion (c.1-?_642+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: The patient had no LOH found in the BAC array CGH data. No variants were found in the tumor tissue.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: M, 36Y0M, Spanish

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: CohortInfo: 7 VHL patients, from different regions of Spain, affected from juxtapapillary or peripheral haemangioblastomas were administered 120 mg propranolol daily.

CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseHPOFreeText: Patient 1 presented with one peripheral tumor in the left eye and one peripheral tumor in the right eye with great exudation. Ophthalmologist wrote in his clinical history “no new lesions/no active lesions” during the visits he attended from January 2015 until December 2015. Moreover, his retinal exudation decreased during the months of treatment with the administration of propranolol.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Information obtained from Table 2.

Variant: c.463+2A>C

LegacyVariant: N/A

CaseProblemVariantFreeText: Amino acid does not coincide with position, declared by the authors. Variant c.463+2A>C could be translated to c.463+2T>C or c.463+3A>C. Needs to be confirmed with the authors.

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: c.463+2A>C

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: 3

KindredID: 3

Case: 31Y0M, Sex unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: None

CasePresentingHPOs:  HP:0010797; HP:0005584; HP:0002666 (hemangioblastoma, renal cell carcinoma, pheochromocytoma)

CaseHPOFreeText: CNS hemangioblastoma first presenting at 24Y, RCC and pheos at 31Y

CaseNotHPOs: HP:0009715 (Papillary cystadenoma of the epididymis)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

GroupID: 32

DiseaseAssertion: assumed VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 2 of the 573 patients discussed in this paper were found to have the following mutation belonging to 1 family. 

GroupPresentingHPOs: HP:0006880; HP:0009711 (cerebellar hemangioblastoma; retinal capillary hemangioma)

GroupHPOFreeText: 1 patient had retinal hemangiomas diagnosed at an unknown age and 1 had cerebellar HB diagnosed at 31Y

GroupNotHPOs: HP:0002666; HP:0005584 (pheochromocytoma; renal cell carcinoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.Y175* (c.525delC) 

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA913185019 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.525del

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: Y175* (c.525delC) 

MultipleGeneVariants: N/A

PatientID: None (proband 12)

KindredID: 12

Case: M, 31Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: Only his mother was mentioned. She was also found with hemangioblastoma at 30Y, however she died before diagnosis; thus no DNA sample available.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: patient had hemangioblastoma of the CNS diagnosed at 31Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E94* (c.280G>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 584477 https://www.ncbi.nlm.nih.gov/clinvar/variation/584477/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: E94* (c.280G>T)

MultipleGeneVariants: N/A

PatientID: 25

KindredID: 15

Case: F, 31Y0M, Indian

DiseaseAssertion: VHL

FamilyInfo: Has relevant family history but details are not made available.

CohortInfo: This retrospective study was conducted at Department of Endocrinology of a tertiary care health centre in Western India. Patients presented to our institute between 2008 and 2016 were included in the study. During the study period a total of 33 patients were suspected to have VHL syndrome based on clinical features among whom 31 patients were found to have mutation in VHL gene. All patients are of Asian Indian descent.

CasePresentingHPOs: HP:0002666; HP:0010797; HP:0001737; HP:0030405 (Pheochromocytoma, Hemangioblastoma, Pancreatic endocrine tumor)

CaseHPOFreeText: Unilateral pheochromocytoma.

CaseNotHPOs: HP:0005584; HP:0002668; HP:0009711; HP:0001737 (Renal cell carcinoma, Paraganglioma, Retinal capillary hemangioma, Pancreatic cysts)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98S (c.293A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 219160, https://www.ncbi.nlm.nih.gov/clinvar/variation/219160/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: Y98S (c.293A>C)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: 11

Case: Sex Unknown, 32Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: Patient had family history of VHL disease. Patient’s mother presented with a hemangioblastoma at age 30 but died prior to diagnosis and genetic testing could be done.

CohortInfo: 16 Chinese patients clinically diagnosed with VHL disease.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: The patient presented with a hemangioblastoma at age 31.

CaseNotHPOs: HP:0009711, HP:0002666, HP:0030393, HP:0006770, HP:0001732 (retinal capillary hemangioma, pheochromocytoma, endolymphatic sac tumor, clear cell renal cell carcinoma, abnormality of the pancreas)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E94* (c.280G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 584477, https://www.ncbi.nlm.nih.gov/clinvar/variation/584477/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: E94* (c.280G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 16

Case: Sex Unknown, 31Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The patient's father had a hemangioblastoma of the central nervous system at age 45. He was deceased before diagnosis could occur. The patient's sister, daughter, and nephew were all confirmed to have the same genetic mutation but were asymptomatic.

CasePresentingHPOs: HP:0010797, HP:0005584, HP:0001732 (hemangioblastoma, renal cell carcinoma, abnormality of the pancreas)

CaseHPOFreeText: The patient presented with hemangioblastoma at age 18. Later at age 31, he/she presented with renal cell carcinoma and pancreatic cysts or tumours.

CaseNotHPOs: HP:0009711, HP:0002666, HP:0009715 (retinal capillary hemangioma, pheochromocytoma)

CaseNotHPOFreeText: The patient did not have epididymal or ovarian cystadenoma.

CasePreviousTesting: N/A

PreviouslyPublished:29330336

Variant: Exon 1 deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1 Deletion

MultipleGeneVariants: N/A

PatientID: None

KindredID: 7

Case: Unknown, 31Y0M, Chinese

DiseaseAssertion:VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0010797, HP:0005584, HP:0001732, HP:0002666 (hemangioblastoma, renal cell carcinoma, abnormality of the pancreas, pheochromocytoma)

CaseHPOFreeText:The patient presented with hemangioblastoma and pheochromocytoma at age 30. One year later he was found to have renal cell carcinoma and pancreatic cysts or tumors.

CaseNotHPOs: HP:0009711(retinal capillary hemangioma)

CaseNotHPOFreeText: No epididymal/ovarian cystadenomas.

CasePreviousTesting: N/A

PreviouslyPublished: 29330336

Variant: p.V130L (c.388G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2229 https://www.ncbi.nlm.nih.gov/clinvar/variation/2229/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: V130L (c.388G>C)

MultipleGeneVariants: N/A

PatientID: 93

KindredID: 30

Case: M, 31Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; (Hemangioblastoma)

CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at age 51.

CaseNotHPOs: HP:0002666; HP:0009711; HP:0005584; HP:0001737; HP:0001732 (Pheochromocytoma, Retinal capillary hemangioma, Renal cell carcinoma, Pancreatic cysts, Abnormality of the pancreas)

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.E94* (c.280G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 584477; https://www.ncbi.nlm.nih.gov/clinvar/variation/584477/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: E94* (c.280G>T)

MultipleGeneVariants: N/A

PatientID: 276

KindredID: 107

Case: M, 50Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband, patient 276, presented with a retinal angioma at age 31, and a CNS hemangioblastoma and multiple pancreatic cysts/tumors at age 37. The proband has a father who presented with a CNS hemangioblastoma at age 50.

CasePresentingHPOs: HP:0001737; HP:0001732; HP:0010797 HP:0009711 (Pancreatic cysts, Abnormality of the pancreas, Hemangioblastoma, Retinal capillary hemangioma)

CaseHPOFreeText: The proband's father presented with a CNS hemangioblastoma at age 50.

CaseNotHPOs: HP:0002666; HP:0005584 (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: Exon 2-3 Deletion (c.341-?_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 2-3 Deletion

MultipleGeneVariants: N/A

PatientID: 153

KindredID: 56

Case: F, 31Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711; HP:0001737; HP:0001732 (Retinal capillary hemangioma, Pancreatic cysts, Abnormality of the pancreas)

CaseHPOFreeText: The proband presented with a retinal angioma at 26, and multiple pancreatic cysts/tumors at 31.

CaseNotHPOs: HP:0010797; HP:0002666; HP:0005584 (Hemangioblastoma, Pheochromocytoma, Renal cell carcinoma)

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.I151N (c.452T>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351754356; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA351754356

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: I151N (c.452T>A)

MultipleGeneVariants: N/A

GroupID: 6B

DiseaseAssertion: assumed VHL

GroupSize: 9

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Chinese

GroupAgeRange: 33.8Y +/- 17.6Y

GroupInfo: Clinical characteristics of 258 patients from 80 unrelated Chinese families were reported in this study. Grouped by the 21 mutations found, 3 families with 13 members total were described. it is unclear how many distinct families are reported in group 6B. 9 individuals were described. Phenotypic information was given for this mutation.

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: 7 of the 9 members presented with CNS hemangioblastoma (mean age of 29.9Y), 2/9 had retinal angiomas at 25Y and 35Y, 1 had renal cell carcinoma (at 30Y), pancreatic cysts in 2 members (with an age of onset of 30 and 31Y), and 1 member with a genital system tumor (epididymis or broad ligament) at 24Y

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: No patients were given with pheochromocytoma

GroupPreviousTesting: N/A

PreviouslyPublished: 29330336; 28388566

SupplementalData: N/A

Variant: p.W88S (c.263G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2220, https://www.ncbi.nlm.nih.gov/clinvar/variation/2220/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W88S (c.263G>C)

MultipleGeneVariants: N/A

PatientID: 93 (First cousin once removed)

KindredID: 18

Case: M, 31Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: 11 members of this family tested positive for the c.712C>T/c.499C>T germline variant of the VHL gene. 14 members of this family were assumed to carry this variant due to family history/personal medical history. Members of this family range from asymptomatic to multi-organ involvement (pheochromocytoma, pancreatic and renal cysts/tumors and hemangioblastomas). The family was previously reported in PMID 3942913.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: This patient presented with pheochromocytoma (31Y). Patient died at 31Y.

CaseNotHPOs: HP:0005584; HP:0000077; HP:0001732; HP:0009711; HP:0010797 (Renal cell carcinoma, Abnormality of the kidney, Abnormality of the pancreas, Retinal capillary hemangioma, Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 3942913 (some members of this family are previously reported (phenotypes only) but unable to match patients across papers with confidence)

SupplementalData: Supplementary Table 1.

Variant: N/A

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Authors state that the c.712C>T germline familial variant of the VHL gene in this patient is “inferred from the family”. No genetic testing was done on this patient to confirm this. Being that this familial variant is out of bound with respect to the NM_000551.3 reference sequence, it was concluded that this variant is noted in the Latif et al. (1993) reference and was translated to c.499C>T (NM_000551.3).

MutationType: N/A

CivicName: N/A

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: M, 31Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Mother with the same variant and presented with breast cancer at age 46 and cerebellar hemangioblastoma and renal cell carcinoma both at age 54. Maternal grandfather (id: 3) presented with cerebellar hemangioblastoma at age 65. Maternal great-uncle (id: 4) presented with prostate cancer at age 65. Maternal great-grandfather (id: 5) presented with cerebellar hemangioblastomas at age 69. Maternal grandmother and sister did not have the mutation. His maternal grandfather was not tested. No family history of retinal capillary hemangiomas or pheochromocytoma.

CasePresentingHPOs: HP:0006880; HP:0009713; HP:0005562 (Cerebellar hemangioblastoma, Spinal hemangioblastoma, Multiple renal cysts)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Figure 1 (pedigree) and Table 1 (phenotype and age of onset data).

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: Germline, FANCD2, Partial Deletion

PatientID: 40

KindredID: 3488

Case: F, 31Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

CaseHPOFreeText: She presented with one pathologic pancreatic endocrine tumour.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: p.R167Q (c.713G>A)

CaseProblemVariantFreeText: N/A

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

CAID: CA020454 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.500G%3EA

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

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500G>A)

MultipleGeneVariants: N/A

GroupID: 6

Case: 31Y0M, 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.182_185delCCGT) was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0009711; HP:0006880 (retinal capillary hemangioma; cerebellar hemangioblastoma)

CaseHPOFreeText: patient had retinal capillary hemangioma diagnosed at 31Y and cerebellar hemangioblastoma diagnosed at 30Y

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.P61Rfs*5 (c.182_185delCCGT)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA658820712 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.182_185del

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: P61FS (c.182_185delCCGT)

MultipleGeneVariants: N/A

This part is troubling because it shows that the narrator feels pressure to change herself to fit into American culture. She believes that her original way of speaking is not acceptable, which may lead to a loss of her identity.

This part is interesting because it shows the difference between Chinese and American communication styles. In Chinese culture, speaking loudly is normal, but in American culture, it may be seen as rude. This highlights the cultural conflict the narrator experiences.

This part is interesting because it shows that starting from nothing can actually give a person more motivation. When he says he has nothing to lose, it means he is not afraid of failure, which makes him more confident and determined.

This part is troubling because even though he looks ready, he is actually very nervous and keeps forgetting.

This part is interesting because it asks whether the exchange program helps or hurts public school students, which shows the difference between schools.

Guilt becomes permanent, he will never be at peace again.

The weapon seem to guide him, as if fate is pushing him him.

He shifts responsibility away from himself.

This part is interesting because Macbeth starts to question his own vision, which shows his inner conflict.

His kindness and generosity were often misunderstood by others.

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

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

80 Years Later, Are We Still on ‘The Road to Serfdom’? by [[Rainer Zitelman]]

Ref. by PM

The Choice this Election is between Corporate and Oligarchic Power by [[Chris Hedges]]

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

https://www.kleinezeitung.at/steiermark/19207990/der-klimaschutz-weicht-den-interessen-der-autofahrer

Studien zeigen, dass BECCS (Bioenergie mit CO₂-Abscheidung und -Speicherung) theoretisch CO₂ aus der Atmosphäre entfernen könnte, aber erhebliche Risiken birgt. Kritiker warnen, dass BECCS eine Scheinlösung sein könnte, da sie hohe Kosten, ökologische Nachteile und einen enormen Flächenbedarf hat. Der Weltklimarat (IPCC) betont die Notwendigkeit zusätzlicher CO₂-Entfernungstechnologien, doch BECCS ist in großem Maßstab kaum erprobt. Experten wie der Vorsitzende des Umweltlenkunsgremiums des Zusammenschlusses von Europas Wissenschaftsakademien (EASAC), die NGO Fern, und das britische Politikinstitut Chatham House weisen auf die Unzuverlässigkeit und die Gefahr der Überschätzung von BECCS hin, was zu verzögerten Emissionsminderungen führen könnte. https://www.dw.com/de/beccs-biomasse-kraftwerke-mit-co2-speicherung-bluff-oder-klimarettung/a-63557343 [Zusammenfassung: generiert mit Mistral und redigiert]

Die französischen Wälder verliere die Fähigkeit CO2 zuabsorbieren, viermal schneller, als in den Planungen der Regierung angenommen. Diese Veränderungen sind folgende globalen Erhitzung. Sie gefährden die bisherigen Zielsetzungen Frankreichs zur CO2-Neutralität, weil der Wald bei weitem nicht in dem Ausmaß als Senke zur Verfügung steht, wie dort vorgesehen.

https://www.liberation.fr/environnement/climat/la-foret-francaise-un-puits-de-carbone-bientot-a-sec-20230531_736OXSN6AZHDLF3GNTZELEKDGA/

https://www.liberation.fr/environnement/tempetes-ouragans-pluies-torrentielles-ce-sont-des-rappels-tragiques-de-notre-nouvelle-realite-climatique-20241031_74QP7OSRIFAR3AHIT336GRJQMQ/

https://www.derstandard.at/story/3000000255243/weil-milliardenschwere-heiztauschfoerderungen-vorzeitig-auslaufen-schlaegt-die-branche-alarm

for - from - Telegram discussion with Gyuri - IndyWiki channel - 2025, Jan 31 - search - Google - word similiarity attention intention - to - search - Google - interesting results returned - word similiarity attention intention - Attending to Attention and Intention Etymonline advises that words like tend, attend, intend, attenuate, obtain, retain, sustain, extend, -

Der französische Klimatologe Robert Vautard stellt fest, dass die Temperaturen des Jahr 2024 noch stärker als 2023 vom Erwartet abgewichen sind. Seit zwei Jahren erlebe der Planet einen zusätzlichen Fieberschub. Die Gründe seien noch nicht geklärt, die Reduzierung der Reflexion von Sonneneinstrahlung durch die Abnahme des arktischen und antarktischen Meereises spiele wahrscheinlich eine Rolle. https://www.liberation.fr/environnement/climat/rechauffement-pour-le-copresident-du-giec-2024-a-ete-encore-plus-hors-norme-que-2023-et-cela-pose-beaucoup-de-questions-20241231_Q4A5ZQBEBRHWREZIY3UYGSFEFM/?redirected=1

Science-Studie zur Abnahme der Albedo der Erde: https://www.science.org/doi/10.1126/science.adq7280

Find out more! What was the Battle of Sitka? What was the outcome?

Cite your source(s!)

https://www.theguardian.com/environment/2024/oct/31/eu-emissions-fall-by-8-in-steep-reduction-reminiscent-of-covid-shutdown

Bericht: https://www.eea.europa.eu/en/analysis/publications/trends-and-projections-in-europe-2024

Only our own work? Maybe also that of our friends, of our communities, etc.?

What if the backend itself is hosted in a distributed way? E.g. based on, or extending, protocols such as ipfs/hypercore.

https://typewriterdatabase.com/19xx-olivetti-eton.23086.typewriter

Sounds right, but double check https://new.reddit.com/r/typewriters/comments/1e8r1vi/olivetti_dora/

DOI: 10.18699/VJGB-23-31

Resource: RRID:BDSC_67946

Curator: @olekpark

SciCrunch record: RRID:BDSC_67946

What is this?

Seit dem Pariser Abkommen finanzierten die 60 größten Banken 425 fossile Großprojekte - sogenannte carbon bombs mit einem zu erwartenden CO2-Ausstoß von jeweils über einer Gigatonne - mit insgesamt 1,8 Billionen Dollar. Der Standard-Artikel geht auf ein Projekt zurück, bei dem Daten des Carbon Bombs-Projekts, des Global Energy Monitor und von Banking on Climate Chaos ausgewertet und visualisiert werden. https://www.derstandard.at/story/3000000193065/billionenkredite-fuer-fossile-grossprojekte-wie-banken-die-klimakrise-mitfinanzieren

Bericht/Visualisierung: https://www.carbonbombs.org/

In Frankreich war der Monat Juli 0,8 Grad wärmer als im Durchschnitt. Es handelt es sich um den 18 überdurchschnittlich warmen Monat infolge. Nach wie vor ist Frankreich vor allem von Trockenheit betroffen. für mehr als 30 Departements wurde eine Krisensituation ausgerufen. Der Hauptgrund dafür ist, dass ich im vergangenen trockenen Winter das Grundwasser nicht ausreichend regenerieren konnte. https://www.liberation.fr/environnement/climat/malgre-la-fraicheur-qui-sannonce-la-secheresse-continue-de-setendre-20230731_6NOOMQZZ5VAKJO57QUKV73YRQE/

Gut recherchierter Überblicksartikel zur zunehmenden Ausbeutung von Erdgas im Senegal und Ländern. https://www.washingtonpost.com/world/2024/01/31/senegal-natural-gas-climate-change/

Deutsche Politiker:innen fordern bessere Voraussetzungen für Erdgasförderung in Deutschland. Begründung ist die Entscheidung der Biden-Adminstration, die Klimafolgen des geplanten EC2-Terminals vor einer Genehmigung zu prüfen, die als Moratorium interpretiert wird. Expert:innen gehen von einer deutlichen Steigerung des LNG-Angebots in den kommenden Jahren aus. https://www.handelsblatt.com/unternehmen/energie/fluessigerdgas-stopp-neuer-lng-exporte-das-bedeutet-bidens-entscheidung-fuer-deutschland/100010499.html

Bericht über eine Diskussion mit Aktivisten und einer Vertreterin der Pariser Bürgermeisterin zur écologie populaire (Ökologie des Volks). Die Veranstaltung gehörte zur von der Libération veranstalteten Climat Libé Tour. Entscheidend ist der Gedanke,dass sich, wenn man von den Lebensbedingungen ausgeht, nicht zwischen ökologischen und sozialen Fragen unterscheiden lässt. Das spielt zum Beispiel eine Rolle bei der Forderung nach qualitätvoller lokaler Lebensmittelversorgung. https://www.liberation.fr/forums/il-ny-a-aucune-difference-entre-justice-sociale-et-justice-climatique-au-climat-libe-tour-reflexions-autour-dun-front-commun-20240331_CL6W4SBSJNFOLCYOSLEHB5AMJE/

https://app.thebrain.com/brain/3d80058c-14d8-5361-0b61-a061f89baf87/21b90ebd-dd91-4e3d-b58f-b1a77194f9b2

https://www.theguardian.com/environment/2024/jan/31/raw-materials-extraction-2060-un-report

Bericht über die Präsentation der energiestrategie des Burgenlands: Das Burgenland soll bis 2030 klimaneutral werden. Ein zentrales Tätigkeitsfeld der Energie Burgenland ist dabei die Vergrößerung der Speicherkapazität, bei der man auf unterschiedliche Lösungen, unter anderem auch auf Elektroautos als Energiespeicher, setzt. Für großspeicher möchte man die Organic-Solid-Flow-Technologie verwenden. https://www.derstandard.de/story/3000000205472/300-mwh-energiespeicher-sollen-das-burgenland-energieunabhaengig-machen

Katharina Rogenhofer gab die Gründung des Kontext-Instituts für Klimafragen bekannt. Das Institut soll vor allem analysieren, welche politischen Prozesse dazu führen, dass wissenschaftliche Erkenntnisse in der Klimapolitik nicht umgesetzt werden. Eine gleichzeitig publizierte Umfrage ergibt, dass 70% der Österreicher:innen der Meinung sind, dass einzelne Politiker in der Klimapolitik zu sehr von Enzelinteressen ausgehend Entscheidungen treffen. https://www.derstandard.de/story/3000000205152/werden-loesungen-im-klimaschutz-aktiv-verhindert-deutliche-mehrheit-sagt-ja

TotalEnergies kauft der OMV den 50%igen Anteil an der Firma Sapura OMV in Malaysia ab. https://www.derstandard.de/story/3000000205475/omv-verkauft-malaysia-beteiligung-um-903-millionen-dollar

Die Libération empfiehlt angesichts der Klimakrise und mit Hinweis auf die Proteste von Bäuer:innen ein Buch, in dem David Djaïz und Xavier Desjardins für eine macchiavellistisch durchgeführte Revolution durch die Institutionen eintreten, für die das Vertrauen einen großen Mehrheit nötig ist. https://www.liberation.fr/politique/crise-agricole-et-ecologie-la-revolution-obligee-une-lecture-recommandee-20240131_LD33HPW6UZGEDHTAFZKSTPOJDM/

https://azorion.tripod.com/whorf.htm<br /> The (Hopi) World According to Whorf -- a Brief Note<br /> by Gary A. David, 2004

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

eggcorn: ambergrease

https://www.hellingerinstitute.com/what-is-family-constellations/

https://anagora.org/nuggets

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

Ben started at ProPublica on 2024-01-24<br /> https://www.propublica.org/atpropublica/propublica-hires-first-senior-director-for-technology'

See also: https://www.propublica.org/people/ben-werdmuller

Seit 2000 sind mindestens 4 Millionen Menschen direkt an Folgen der globalen Erhitzung gestorben. Diese Minimalschätzung in einer neuen Studie begründet, die globale Erhitzung schon jetzt als Gesundheitsnotstand zu behandeln. https://www.repubblica.it/green-and-blue/2024/01/31/news/negli_ultimi_ventanni_la_crisi_del_clima_ha_causato_4_milioni_di_morti-422021774/

Eine Studie zeigt, dass die CO2-Emissionen deutscher Neuwagen 14,1% höher sind, als es die Hersteller angeben. 2018 lag der Unterschied durchschnittlich bei 7,7%. https://taz.de/CO2-Werte-neuer-Fahrzeuge/!5985888/

Das Ziel der CO₂-Neutralität bis 2040 kann in Österreich mit unterschiedlich Strategien erreicht werden, wir zwei Studien des Grazer Wegener Centers und der WU Wien ergeben. Dazu wurden drei Szenarien entwickelt, von denen eines vor allen auf Technologie, eines auf Kreislaufwirtschaft und eines auf JustTransition setzt. Am teuersten wäre das Technologie-orientierte Szenario. https://www.derstandard.de/story/3000000205462/drei-wege-f252hren-214sterreich-zur-netto-null-bei-den-treibhausgasen

Kurzer und verwirrter Artikel zum australischen Kohlereichtum. Einerseits wird behauptet, dass Australien den weltweit höchsten CO2-Ausstoß pro Kopf habe. Andererseits wird auf seine potenzielle Rolle bei der globalen Energiewende hingewiesen, allerdings ohne Fakten zu benennen. https://www.derstandard.at/story/3000000200974/kohle-bringt-kohle