PatientID: 6

KindredID: 3

Case: F, 37Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: No family information was provided for this patient. A total of 291 patients from 115 different families were included for analysis. VHL mutation confirmation was verified in at least one patient of each family.

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

CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at age 34. At age 37, they presented with renal cell carcinoma and multiple pancreatic cysts/tumors.

CaseNotHPOs: HP:0009711; HP:0002666; (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.S65W (c.194C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43597, https://www.ncbi.nlm.nih.gov/clinvar/variation/43597/

CAID:

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: 187

KindredID: 72

Case: M, 67Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband, patient 72, has multiple family members with the same mutation. Her father (patient 73) had a CNS hemangioblastoma at 65, renal cell carcinioma at 54, and multiple pancreatic cysts/tumors at 67. Her sister 2 (second sister) had multiple pancreatic cysts/tumors at 36, and a CNS hemangioblastoma at 39. Her sister 3 had multiple pancreatic cysts/tumors at 32, and a retinal angioma at 34. The proband's sister 1 had a CNS hemangioblastoma at 22, but passed away before they could be diagnosed/ confirmed with the mutation.

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

CaseHPOFreeText: The patient presented with a CNS hemangioblastoma at 65, renal cell carcinoma at 54, and multiple pancreatic cysts/tumors at 67.

CaseNotHPOs: HP:0009711; HP:0002666 (Retinal capillary hemangioma, 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.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

PatientID: 1

KindredID: 1

Case: Sex Unknown, 40Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0006770, HP:0001732, HP:0010797 (clear cell renal cell carcinoma, abnormality of the pancreas, hemangioblastoma)

CaseHPOFreeText: The patient presented with a hemangioblastoma at age 34, clear cell renal cell carcinoma at age 37, and abnormality of the pancreas at age 37.

CaseNotHPOs: HP:0009711, HP:0002666, HP:0030424, HP:0030393 (retinal capillary hemangioma, pheochromocytoma, epididymal cyst, endolymphatic sac tumor)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S65W(c.194C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43597 https://www.ncbi.nlm.nih.gov/clinvar/variation/43597/

CAID: CA020099 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.194C%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName:S65W(c.194C>G)

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: 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