PatientID: 2368

KindredID: 2368

Case: M, 61Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Patient has no family history of VHL disease.

CasePresentingHPOs: HP:0006770 (clear cell renal cell carcinoma)

CaseHPOFreeText: The patient presented with renal cell carcinoma (please see supplementary data 1)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: See supplementary data 1.

Variant: p.E21A (c.62A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 411957, https://www.ncbi.nlm.nih.gov/clinvar/variation/411957/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: E21A (c.62A>C)

MultipleGeneVariants: N/A

PatientID: 43

KindredID: 15

Case: F , 21Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: Proband (patient 42) has four family members confirmed with the mutation, and two family members who passed away before diagnosis/ genetic confirmation of the mutation. Family members confirmed with the mutation include: the proband's daughter (patient 43) who had retinal angioma (age 17), renal cell carcinoma (21), multiple pancreatic cysts/tumors (18), and a pheochromocytoma (19). His son (patient 44) who was asymptomatic at the time of assessment. His niece 1 (patient 47) who had a retinal angioma and renal cell carcinoma (22). And his niece 2 (patient 28) who had a CNS hemangioblastoma (19) and a retinal angioma (18). Family members who passed away before diagnosis and were not genetically confirmed include: his sister (oatient 45) who had a CNS hemangioblastoma (22), and his brother (patient 46) who had a retinal angioma and renal cell carcinoma at 52.

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

CaseHPOFreeText: The proband's daughter (patient 43) presented with retinal angioma at 17, multiple pancreatic cysts/tumors at 18, pheochromocytoma at 19, and renal cell carcinoma at 21.

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.S80Tfs*77 (c.239_245del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA913189246; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.239_245del

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: S80fs (c.239_245del)

MultipleGeneVariants: N/A

PatientID: IP (Proband)

KindredID: E

Case: M, 21Y0M, Hungarian

DiseaseAssertion: VHL

FamilyInfo: Index patient was a 21-year-old man who had bilateral renal masses and renal cysts. Family history indicated a high suspicion for VHL disease, as his mother was operated for renal cell carcinoma, his uncle had spinal cord tumor, and his grandmother underwent operation for renal cell carcinoma. However, detailed clinical evaluation could not be performed in family members.

CasePresentingHPOs: HP:0005584; HP:0005562 (Renal cell carcinoma, Multiple renal cysts)

CaseHPOFreeText: Presented with bilateral highly vascularized renal masses and a large number of renal cysts. Diagnosed with VHL Type 1. Renal masses are noted as renal cell carcinoma in Table 1.

CaseNotHPOs: HP:0002666; HP:0009711; HP:0010797 (Pheochromocytoma, Retinal capillary hemangioma, Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F119Qfs*12 (c.354_355del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA915940709, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.354_355del

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion; minus_2_frameshift_variant

CivicName: F119fs (c.354_355del)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: F, 35Y0M, Japanese

DiseaseAssertion: VHL

FamilyInfo: No relevant family history - speculated de novo but did not perform genetic testing of family members

CasePresentingHPOs: HP:0002894; HP:0005584; HP:0006880 (pancreatic neoplasm; renal cell carcinoma; hemangioblastomas of the cerebellum)

CaseHPOFreeText: A 35Yo woman became aware of a tumour - giant masses in the whole pancreas and a tumor of the right kidney - after giving birth to a healthy boy. History of cerebal hemangiomas treated by surgery 14Y previously (at 21 years old). (serous cystic neoplasms pancreas; Right renal cell carcinoma; hemangioblastomas of the cerebellum)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N78I (c.233A>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223169 https://www.ncbi.nlm.nih.gov/clinvar/variation/223169/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: N78I (c.233A>T)

MultipleGeneVariants: N/A

PatientID: proband 17

KindredID: 17

Case: M, 21Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: the patients mother was found at 43Y with RCC and multiple pancreatic cysts or tumors, however she passed before any diagnosis of DNA sample was provided

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

CaseHPOFreeText: patient was found with retinal hemangioblastomas and epididymal/ovarian cystadenoma at 21Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: exon 1 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 1 deletion

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 32Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: Many of the patient’s family members developed lesions in sites suggesting VHL including multiple central nervous system tumours (probable hemangioblastomas), renal tumours (probable renal cell carcinomas), pancreatic tumours (probable cysts and neuroendocrine tumours), temporal bone tumours (probable ELST), and some of the family members have lost their sight because of retinal detachment (probably in the case of retinal haemangiomas). However, the diagnosis of VHL has not been established in the family. Two of his children were also found to have the NM_000551.3:c.194C>T(S65L) mutation after analysis of blood samples.

CasePresentingHPOs: HP:0030393; HP:0010797; HP:0009711 (Endolymphatic sac tumour, hemangioblastoma, retinal capillary hemangioma)

CaseHPOFreeText: The patient had a history of left facial nerve palsy at the age of 19 years due to tumour of the temporal bone with a recurrence two years later (at 21Y). The patient was originally histopathologically diagnosed with choroid plexus papilloma, but was re-diagnosed with an endolymphatic sac tumour on reexamination of the sample. Three years later (24Y) the patient developed ataxia because of a cerebellar tumour that was histopathologically diagnosed as hemangioblastoma. He had a recurrence two years later (26Y). He also had a history of retinal capillary angioma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S65L (c.194C>T)

LegacyVariant: p.S65L (c.407C>T)

ClinVarID: 182975, https://www.ncbi.nlm.nih.gov/clinvar/variation/182975/

gnomAD: 0.000, https://gnomad.broadinstitute.org/variant/3-10183725-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: S65L(c.194C>T)

MultipleGeneVariants: N/A

PatientID: II.1

KindredID: 2

Case: M, 21Y0M, Ethnicity Unknown

DiseaseAssertion: Polycythemia

FamilyInfo: Positive family history. Biologic material from parents were unavailable but Chuvash core haplotype analysis demonstrated that all patients were compound heterozygous, with 1 mutation being inherited from each parent. See Figure 2B for family pedigree.

CohortInfo: Patients with Chuvash polycythemia for whom VHL R200W had been found in a heterozygous state

CasePresentingHPOs: HP:0001901 (Polycythemia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.340+770T>C

LegacyVariant:N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 816685 https://www.ncbi.nlm.nih.gov/clinvar/variation/816685/

CAID: N/A

gnomAD: 0.00003186 https://gnomad.broadinstitute.org/variant/3-10184641-T-C

VariantEvidence: N/A

MutationType: intron_variant

CivicName: c.340+770T>C and R200W (c.598C>T)

MultipleGeneVariants: Germline, VHL, c.598C>T (p.Arg200Trp)

PatientID: 6

KindredID: 6

Case: F, 21Y6M, ethnicity unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: Positive history, with symptomatic father (no mutation known)

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.464-1G>T

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 223221 https://www.ncbi.nlm.nih.gov/clinvar/variation/223221/

CAID: N/A

gnomAD: N/A

VariantEvidence: Compound heterozygous: Germline C to G base change at nucleotide 150 of exon 1, and G to T base change at -1 position of splice acceptor sequence for exon 3

MutationType: splice_site_variant

CivicName: [A50= (c.150C>G) and] Splice Site (c.463-1G>T)

MultipleGeneVariants: Germline, VHL, c.150C>G (p.Ala50Ala)

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: 8

KindredID: 5

Case: M, 30Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband's grandfather, father, and uncle presented with a CNS hemangioblastoma at ages 30, 36, and 33, respectively, and all passed away before they could be diagnosed with VHL disease.

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

CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at age 21 and a multiple pancreatic cysts/tumors at age 30.

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

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.S65L (c.194C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182975; https://www.ncbi.nlm.nih.gov/clinvar/variation/182975/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: S65L(c.194C>T)

MultipleGeneVariants: N/A

PatientID: 136

KindredID: 51

Case: M, 25Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband (patient 136) has a mother (patient 137) who presented with a CNS hemangioblastoma at 32, and renal cell carcinoma/ pheochromocytoma at 38. However, no DNA sample was available for his mother's genetic testing.

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

CaseHPOFreeText: The proband (patient 136) presented with multiple pancreatic cysts/tumors at 21, renal cell carcinoma at 23, and a CNS hemangioblastoma at 25.

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.P146Gfs*14 (c.435_436ins)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2573131810, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2573131810

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_2_frameshift_variant

CivicName: P146Gfs*14 (c.435_436insGG)

MultipleGeneVariants: N/A

PatientID: 149 (Half first cousin once removed)

KindredID: 18

Case: M, 57Y0M, 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:0009711; HP:0002666 (Retinal capillary hemangioma, Pheochromocytoma)

CaseHPOFreeText: This patient presented with retinal angioma (21Y) and pheochromocytoma (21Y).

CaseNotHPOs: HP:0005584; HP:0000077; HP:0001732; HP:0010797 (Renal cell carcinoma, Abnormality of the kidney, Abnormality of the pancreas, 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: 11

KindredID: 2

Case: M, 21Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Patient has 2 siblings (patients 10 and 12) with the same mutation and pheochromocytoma.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Bilateral pheochromocytoma (40mm and 30mm)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: SDHB (NM_003000.2), SDHC (NM_003001.3), SDHD (NM_003002.2), SDHAF2 (NM_017841.2), RET (exons 10–11 and 13–16, NM_020975.4), TMEM127 (NM_017849.3), MAX (NM_002382.3).

PreviouslyPublished: N/A

SupplementalData: Table 2

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

VariantEvidence: Loss of heterozygosity could be detected in tumour DNA.

MutationType: missense_variant;transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: F, 47Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: No family history.

CasePresentingHPOs: HP:0006880; HP:0002894; HP:0005584 (Cerebellar Hemangioblastoma; neoplasm of the pancreas; renal cell carcinoma)

CaseHPOFreeText: At 35-year old, the female patient was diagnosed with VHL due to clinical presentation of pancreatic serous cystic neoplasm and renal cell carcinoma, and cerebellar hemangioblastomas that were surgically removed at age 21. The patient had underwent total pancreatectomy and right nephrectomy for pancreatic serous cystic neoplasm (SCN) and renal cell carcinoma (RCC), respectively. 4 years later, tumors in the liver were detected by CT scan and radiographically diagnosed as metasta-ses of the pancreatic SCN or RCC. Again, morphology and immunohistochemical findings of the resected tumors again were similar to the primary pancreatic SCN, thus diagnosed as multiple metachronous liver metastases of pancreatic SCN. As of 47Y, the patient has remained disease-free without any recurrence after the third operation.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 21673464

SupplementalData: N/A

Variant: p.N78I (c.233A>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223169 https://www.ncbi.nlm.nih.gov/clinvar/variation/223169/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: N78I (c.233A>T)

MultipleGeneVariants: N/A

PatientID: 11 (Father)

KindredID: 7

Case: M, 39Y0M, 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 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 1 presented with pheochromocytoma. ID 2 presented with pancreatic abnormalities. ID 10 presented with CNS hemangioblastoma, pancreatic abnormalities and pheochromocytoma. ID 4 presented with pheochromocytoma.

CasePresentingHPOs: HP:0002666; HP:0000077; HP:0001732 (Pheochromocytoma, Abnormality of the kidney, Abnormality of the pancreas)

CaseHPOFreeText: The patient presented with renal and pancreatic cyst or tumor (unspecified) (33Y), pheochromocytoma (21Y) and other undefined phenotypes (33Y).

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

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: III-3

KindredID: 1

Case: M, 25Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Both of the patient’s uncles (Patient II-1 and II-4) were clinically diagnosed with VHL disease, and carried the mutation NM_000551.3:c.269A>T. Patient II-1 presented with RCCC at age 33 and cerebral hemangioblastoma at age 41. Patient II-4 presented with RCCC at age 53. The patient’s deceased father (Patient II‐3) and deceased aunt (Patient II‐5) were also clinically diagnosed with VHL disease, but the mutation was undetermined before death. His father died of advanced RCCC, and his aunt (Patient II‐5) died of a ruptured CH. The patient’s grandparents (Patient I-1 and I-2) were also deceased from other causes. The patient’s son (Patient IV‐1), wife (Patient III‐2), and mother (Patient II‐2) were healthy and did not carry the mutation. Their annual physical examination did not reveal a hemangioblastoma, kidney mass or abdominal cyst.

CasePresentingHPOs: HP:0006880 (Cerebellar hemangioblastoma)

CaseHPOFreeText: The 25Y male patient presented with occipital headache at 21Y. Upon initial examination, the patient was diagnosed with cerebellar hemangioblastoma and the tumour was resected. The patient completed outpatient follow‐up three years later. The occipital headache had disappeared, brain MRI showed no recurrence, and abdominal CT revealed no neoplasms.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N90I (c.269A>T)

LegacyVariant: N/A

ClinVarID: 223172, https://www.ncbi.nlm.nih.gov/clinvar/variation/223172/

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: N90I(c.269A>T)

MultipleGeneVariants: N/A

PatientID: 155

KindredID: 58

Case: M, 26Y0M, 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:0009711; HP:0001737; HP:0001732; HP:0005584 (Retinal capillary hemangioma, Pancreatic cysts, Abnormality of the pancreas, Renal cell carcinoma)

CaseHPOFreeText: The proband presented at age 21 with retinal angioma, and at age 26 with multiple pancreatic cysts/tumors and renal cell carcinoma.

CaseNotHPOs: HP:0010797; HP:0002666 (Hemangioblastoma, Pheochromocytoma)

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

GroupID: 15

Case: 23Y0M, 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 was found in 1 VHL family with a single patient.

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

CaseHPOFreeText: patient had retinal angiomas at 21Y and cerebellar hemangioblastomas diagnosed at 23Y

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.F91* (c.272_273delinsAA)

CaseProblemVariantFreeText: c.272T>A and c.273C>A results in c.272_273delinsAA

LegacyVariant: N/A

ClinVarID: CA2499307077 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499307077

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: delins; stop_gained

CivicName: F91* (c.272_273delinsAA)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: M, 41Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: No family history of VHL disease.

CasePresentingHPOs: HP:0030393; HP:0009711; HP:0010797; HP:0002666; HP:0009726; HP:0001737 (endolymphatic sac tumor, retinal capillary hemangioma, hemangioblastoma, pheochromocytoma, renal neoplasm, pancreatic cysts)

CaseHPOFreeText: patient was 21 years old when he experienced a sudden right hearing loss (cophosis). During a follow-up, the patient suffered from other manifestations of VHL disease mentioned above.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

I was excited when I saw these poetic techniques for the first time. There are so many techniques, such as alliteration, half-lines, and caesura. I also think the people who identified these techniques in such old poems and explained them to us are really impressive.

The cross is no longer seen as an instrument of execution. It's transformed into a symbol of salvation and glory. As I grew up in a church, I heard this several times before. While not until I thought about it again did I realize what a brilliant contrast it was.

It seems she really hates him.

Writing down your current feelings is a great way to express oneself.

When later generations listen to the stories told by their predecessors, only those who truly experienced it can truly understand.

https://www.reddit.com/r/typewriters/comments/1uow243/just_in_case/

https://cesarhidalgo.com/

The Observatory of Economic Complexity (OEC)<br /> https://oec.world/en

https://www.pasadenastarnews.com/2011/01/30/beckmans-influence-name-prominent-at-caltech

for - stats - psychopathy - 3 to 21% in boardrooms and parliaments - more likely to find psychopath in boardroom and parliament than grocery store - SRG comment - stats- shadow side of leadership - high percentage of leaders have dark triad

this represents the conscious effort to go beyond the surface stories 'myths' and confront the deeper, often hidden realities 'the wreck'

I was so suprised that the author uses ladder to represnts the fear of his alone.

I love the author writes about the stress that the author can't support about it.

What is the mask is about? Is a phase or a another thing?

As the author stroke his beam of his lamp on the flank, what he was doing can be looking back the wounds and emotions he had. And it's something that comes and never goes, unlike fish or weed, which doesn't leave lasting impact to our brain.

The speaker finally reached the wreck and become part of it. Calling herself both the mermaid and the merman could suggest that she feels connected to different sides of human experience, not limited by gender.

This part might mean that the speaker’s goal is to truly explore and understand the wreck, not just read about it. The “words” could represent stories or explanations that guide her, like maps, but she still needs to see the truth for herself.

This might describe how the she feels awkward and alone while going deeper into the sea. The image of crawling “like an insect” could suggest weakness or discomfort.

I see nothing in common at this point, and cannot associate the two lines.

I think it’s interesting how the ordinary diving equipment becomes symbolic, like “black rubber body armor” and “awkward mask,” suggesting emotional or psychological protection.

I think when she says it's easy to forget what she came for, it;s because there's so much to take in down there ; not just the wounds and broken things, but also strange , hauntingly beautiful details that make you want to stay and wander.Tat's why there seem to be people who have 'always lived here' - they've settles among the ruins, maybe trapped by it or maybe finding a kind of comfort in it.

I think this is powerful because it shows that we are all part of this search. Even if our names weren't written in the old stories, we can still go down there and see the wreck for ourselves. I think the wreck here might be our traumas or things we try to forgetting. this line is really deep

I love how she describes the wreck so vividly that we can picture it. it makes me think of the dark times in our own lives when we wanted to reach the sunlight so badly. some things we believed would last forever ended up drifting into the 'ocean of lost memories' I especially like the part about the ribs, it feels like those old hurts we try to ignore, but every now and then they poke us again. we can't really erase them ;we just learn to move around them, like tentative haunters of our own past.

the ladder is a symbol of a way into depths of history/memory, but here she wrote 'we who have used it' implying that not everybody chooses descend..Only the ones who choose to climb down can really start to face themselves and hidden truths.

unlike heroic male explorers, the speaker dives alone leads to feminist emphasis on personal, solitary quest

I think the two roads symbolize the choice we all face in life - one may be destiny and the other fate, but no matter which we choose , it leads us to a certain way of living and becoming ourselves.

Her mother's garden symbolizes suppressed female creativity-beauty and art growing from struggle, like magic.

Society once saw creative women as "mad", but their so-called madness is actually passion, vision and art.

https://www.sefaria.org/topics/ben-sorer-umoreh?sort=Relevance&tab=notable-sources The Ben Sorer Umoreh — known in English as the“wayward and rebellious son”

via u/Koponewt (Otto)

Eine Studie aus dem Jahr 2021 zeigt, dass Männer in Schweden 16% mehr klimaschädliche Emissionen verursachen als Frauen, obwohl sie ähnliche Geldbeträge ausgeben. Der Hauptgrund ist der höhere Kraftstoffverbrauch für Autos. Die Studie, veröffentlicht im Journal for Industrial Ecology, ergab, dass über die Hälfte der Emissionen durch Nahrung und Urlaube verursacht werden. Eine pflanzenbasierte Ernährung und Zugreisen könnten die Emissionen um 40% senken. Die EU wurde kritisiert, weil ihr Green Deal geschlechtsspezifische Unterschiede nicht berücksichtigt. [Zusammenfassung mit Mistral generiert] https://www.theguardian.com/environment/2021/jul/21/men-cause-more-climate-emissions-than-women-study-finds

https://www.theguardian.com/us-news/2025/mar/21/oil-protest-activism-greenpeace-dakota-pipeline-verdict

https://www.liberation.fr/environnement/climat/avec-le-rechauffement-climatique-les-irreductibles-glaciers-asiatiques-du-karakoram-et-du-kunlun-flanchent-a-leur-tour-20250321_WVBHZ2V2LNGWHPVB623YL4T3FM/

https://www.derstandard.at/story/3000000253661/die-trump-walze-rollt-macht-der-klimaschutz-jetzt-pause

https://www.nytimes.com/2023/10/21/magazine/climate-anxiety-therapy.html

https://www.theguardian.com/environment/2024/nov/21/us-and-india-lead-g20-on-climate-action-report-says

Tell us more! Who was Mikhail Lomonosov, and what was he doing during this time period?

Cite your source(s)!

for - article - Medium - Translating vision into sound - A deep learning perspectiive - Viktor Toth - 21 April, 2019 - from - search - Google - android app "The Voice" translates images into audio signal - https://hyp.is/OJKKmJ1MEe-TAp_w_0SK_Q/www.google.com/search?q=android+app+%22The+Voice%22+translates+images+into+audio+signal&sca_esv=6fa4053b1bfce2fa&sxsrf=ADLYWIK_UqZZZ9OCRCwH4D6FoSaykbMTpQ:1731013461104&ei=VSstZ4eCBqi8xc8P5KP_kAU&ved=0ahUKEwjHgM3Tj8uJAxUoXvEDHeTRH1IQ4dUDCA8&uact=5&oq=android+app+%22The+Voice%22+translates+images+into+audio+signal&gs_lp=Egxnd3Mtd2l6LXNlcnAiO2FuZHJvaWQgYXBwICJUaGUgVm9pY2UiIHRyYW5zbGF0ZXMgaW1hZ2VzIGludG8gYXVkaW8gc2lnbmFsMggQABiABBiiBDIIEAAYgAQYogQyCBAAGIAEGKIEMggQABiABBiiBDIIEAAYgAQYogRI2xdQpglYjRJwAXgCkAEAmAGZA6ABmQOqAQM0LTG4AQPIAQD4AQGYAgOgAqADwgIKEAAYsAMY1gQYR8ICBBAAGEeYAwDiAwUSATEgQIgGAZAGCJIHBTIuNC0xoAewBA&sclient=gws-wiz-serp

1:21:54 If a community moved to a WELLNESS model rather than an ILLNESS model, it would generate millions of dollars in saved resources 1:21:54 If a community moved to a PREVENTION model rather than a CURE Model, it would generate millions of dollars in resources

1:21:44 By identifying WASTE - we can identify capacity to create VALUE for ALL

https://flux1.ai/examples

for - stats - digital decay - 23% of news webpages contain at least one broken link, - stats - digital decay - 21% of webpages from government sites contain at least one broken link

DOI: 10.1158/0008-5472.CAN-21-3822

Resource: (RRID:CVCL_4784)

Curator: @dhovakimyan1

SciCrunch record: RRID:CVCL_4784

What is this?

DOI: 10.1158/0008-5472.CAN-21-2072

Resource: RRID:Addgene_58779

Curator: @dhovakimyan1

SciCrunch record: RRID:Addgene_58779

What is this?

https://www.literatureandlatte.com/scapple/overview

https://www.jerrymichalski.com/

2024-08-21: JM indicates that he's revamped his personal website.

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

MixedInk was a startup that provided web-based, collaborative writing software enabling large groups of people to create text that expresses a collective opinion, such as a mission statement, editorial, political platform, open letter or product review.

https://www.midjourney.com/home

2024-08-21: PM indicates they're doing free trials now

https://github.com/tweetback

Take ownership of your Twitter data and get your tweets back

https://pinokio.computer/<br /> Pinokio is a browser that lets you install, run, and programmatically control ANY application, automatically.

https://flux1.ai/<br /> Flux AI Image Generator

https://glif.app/glifs

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

DOI: 10.1128/jvi.01778-21

Resource: (BDSC Cat# 3605,RRID:BDSC_3605)

Curator: @mpairish

SciCrunch record: RRID:BDSC_3605

What is this?

https://www.theguardian.com/environment/2024/mar/21/west-africa-heatwave-climate-crisis-study

https://www.liberation.fr/environnement/x-ex-twitter-classe-pire-reseau-social-sur-la-desinformation-sur-le-climat-20230921_2EFGPHKZX5GVXDCCKRHTVMBY2I/

https://www.derstandard.at/story/3000000216598/spoe-will-co2-preis-auf-eis-legen-und-privatjets-verbieten

https://www.theguardian.com/us-news/2024/mar/21/fossil-fuel-companies-homicide-climate-deaths-lawsuit

2024-03-01<br /> $67.99 sale<br /> https://shopgoodwill.com/item/192324052

https://www.nytimes.com/2023/07/21/climate/diet-vegan-meat-emissions.html

Erläuterungen der Energy Charts des Fraunhofer-Instituts für solare Energiesysteme: 2023 kamen 55% des deutschen Strombedarfs aus erneuerbaren Energien, die Kohleverstromung ist deutlich gesunken. Der Verzicht auf Atomkraftwerke war keine Ursache dafür, dass Deutschland in diesem Jahr mehr Strom importierte als exportierte. https://www.handelsblatt.com/unternehmen/energie/strommix-deutschland-so-abhaengig-ist-deutschland-von-stromimporten/100002618.html

Der Standard informiert über zwei Studien, die unter anderem den Zusammenhang von Stadtentwicklung und globaler Erhitzung betreffen. Vor allem in den USA wird für die Mehrzahl der großen Städte eine Schrumpfung vorausgesagt, verstärkt durch die Folgen der Erhitzung. Die Studie verwendet ist Szenarien des IPCC. Unter anderem ergibt sich daraus die Forderung, die Stadtplanung nicht mehr vor allem an der Vorstellung von wachsenden Städten auszurichten. https://www.derstandard.de/story/3000000203501/tausende-us-staedte-koennten-bis-2100-zu-geisterorten-werden

Die österreichischen CO2-Emissionen sind 2023 um etwa 7% gesunken. EU-weit sind die Emissionen um ca 7,4% gefallen, in den USA um 3%. In Indien und China sind sie gestiegen.

Bericht des Wegener Centers: https://wegccloud.uni-graz.at/s/k4DxDgJTKn68QjL

https://www.derstandard.at/story/3000000200637/oesterreichs-treibhausgasausstoss-2023-um-rund-sieben-prozent-gesunken

https://www.nytimes.com/2023/12/21/climate/the-year-in-climate-culture.html

https://www.nytimes.com/2023/12/21/climate/octopus-west-antarctic-ice-sheet.html

Eine neue französische Studie beschäftigt sich mit einer Folge des dramatischen Rückgangs der Insekt. Mangels bestäubender Insekten befruchten sich Pflanzen selbst. Dadurch werden die nächsten Generationen kleiner und liefern weniger Nektar. Es kommt zu einem Rückkopplungseffekt, weil so noch weniger Insekten überleben. In dem Interview mit der liberation erklärt der Biologe diesen Effekt als Beispiel für eine unkontrollierbare und nicht mehr zurücknehmbare, von Menschen ausgelöste Entwicklung. https://www.liberation.fr/environnement/biodiversite/pollinisation-et-disparition-des-insectes-nous-sommes-dans-une-spirale-incontrolable-20231221_CV6BZLN2WJANLN2A2EFUGCJLZI/

https://www.derstandard.de/story/3000000200637/oesterreichs-treibhausgasausstoss-2023-um-rund-sieben-prozent-gesunken

https://www.theguardian.com/environment/2023/nov/21/i-cannot-stress-too-much-about-it-monaco-yacht-buyers-shrug-off-climate-concerns

https://www.theguardian.com/environment/2023/nov/21/the-jet-set-200-celebrities-aircraft-have-flown-for-combined-total-of-11-years-since-2022

https://www.theguardian.com/environment/2023/nov/21/ad-industry-grapples-with-role-selling-consumption-in-climate-crisis

https://www.theguardian.com/environment/2023/nov/21/new-orleans-climate-carbon-emissions

https://www.theguardian.com/science/audio/2023/nov/21/superyachts-and-private-jets-the-carbon-impact-of-the-polluter-elite-podcast

https://www.derstandard.at/story/3000000197439/luftverschmutzung-durch-fossile-energie-sorgt-fuer-mehr-als-fuenf-millionen-todesfaelle

This is an interesting point - can you not profit from PBL if you haven't had the lived experiences of a more privileged studennt?

These insights are based on the research of Jean Anyon. She collected data in 5 different schools, that served particular social classes and noted the differences in how students are taught, based on the social class the school served.

Important point - the way that we have traditionally taught are a reflection of a different world. Yes...there has been that little evolution in how we teach!

this is a contrast to teacher-centered practices

Think back to your SL school's SARC report - is you school serving mostly low-income students?

How do you think this finding impacts other aspects of classroom life - like motivation and classroom management?

This is depressing. Do you feel that this is true about the instruction that you observed in your SL placement?

I wonder how this is related to persistance.

In den Niederlanden wird mit einem Wahlsieg von Parteien gerechnet, die für klimapolitischen Stillstand oder Rückschritt stehen. Die taz beschreibt den Stand der Auseinandersetzungen. Hervorgehoben wird die Stärke der Klimabewegung und die Klimarechtssprechung. Für die meisten Wähler:innen sei Klimapolitik nicht von Verteilungs- und Gerechtigkeitsfragen zu trennen.https://taz.de/Wahlen-in-den-Niederlanden/!5971214/

Roger Hardy erklärt in diesem Artikel über die von ihm in Großbritannien gegründete Organisation Round our Way, dass Arbeiterklassen-Communities von der globalen Erhitzung und ihren Folgen besonders stark betroffen sind und das auch wissen. Nur eine Klimabewegung für "ordinary people" könne das Fundament für einen gesellschaftlichen Konsens über Klimaschutz herstellen. https://www.theguardian.com/environment/commentisfree/2023/nov/21/working-class-people-climate-crisis-policy

61% der Österreicher:innen sprachen sich in einer von Greenpeace in Auftrag gegebenen Umfrage für ein Verbot von Privatflügen aus, 79% für eine Kerosinsteuer, 70% für ein Verbot von Kurzstreckenflügen, wenn alternativ mit der Bahn gefahren werden kann. https://www.derstandard.de/story/3000000196060/mehrheit-in-oesterreich-fuer-privatjet-verbot-und-kerosinsteuer