PatientID: 214

KindredID: 214

Case: Sex Unknown, 33Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None

CasePresentingHPOs: HP:0001737, HP:0010797, HP:0000107 (pancreatic cyst, hemangioblastoma, renal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666, HP:0006770, HP:0009711 (pheochromocytoma, clear cell renal cell carcinoma, retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2, S3.

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history revealed VHL in the father and daughters. Molecular genetic analysis confirmed familial VHL by detecting a mutation of the VHL gene in the patient and his daughters.

CasePresentingHPOs: HP:0009713, HP:0000107( Spinal Hemangioblastoma, Renal Cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant:p.S65W(407C>G)

CaseProblemVariantFreeText: N/A

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

CAID: CA020099 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA020099

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: N/A

KindredID: 1

Case: M, 33Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: Genetic analysis of the patient's parents and brothers, who were unaffected, confirmed a diagnosis of de novo VHL disease.

CasePresentingHPOs: HP:0030424, HP:0009711, HP:0005584, HP:0006770, HP:0001737, HP:0000107 (epididymal cyst, retinal capillary hemangioma, renal cell carcinoma, clear cell renal cell carcinoma, pancreatic cysts, renal cyst)

CaseHPOFreeText: He was admitted to the hospital with a two-month history of progressive right flank pain, accompanied by a one-month history of recurrent painless gross hematuria. The patient's previous medical history included urological surgery at the age of 23 years due to an epididymal cyst and an ophthalmologic surgery at 26 years of age for retinal detachment resulting from bilateral retinal angiomatosis. Contrast-enhanced computed tomography (CT) scanning and angiography were used to detect the presence of quasi-circular enhancing lesions in the middle of the left kidney and large irregular enhancing lesions in the right kidney, extending into the vena cava, that formed an embolus. In addition, multiple cysts in the pancreas and kidney were detected radiologically. The patient underwent a radical nephrectomy with an embolectomy of the right kidney for treatment of T3b-stage renal cell carcinoma. After three months, he successfully underwent laparoscopic nephron-sparing surgery (NSS) of the left kidney. Histological analysis of the renal tissue revealed clear cell carcinomas.

CaseNotHPOs: N/A

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

GroupID: 4325

DiseaseAssertion: assumed VHL

GroupSize: 4

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Familial VHL stated; 4 family members recorded with this mutation.

GroupPresentingHPOs: HP:0010797; HP:0009711 (hemangioblastoma, retinal capillary hemangioma)

GroupHPOFreeText: 1 of the 4 (1/4) patients were recorded with a hemangioblastoma; 3/4 with retinal angiomas

GroupNotHPOs: HP:0002666; HP:0005584 (Pheochromocytoma, renal cell carcinoma)

GroupNotHPOFreeText: None of the patients were recorded to have RCC or pheos

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: p.S65W (c.407C>G)

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

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: F, 6Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history revealed VHL in the father and grandfather. Molecular genetic analysis confirmed familial VHL by detecting a mutation of the VHL gene in the patient, her father, and her sister. Magnetic resonance imaging revealed spinal hemangioblastomas and kidney cysts in the father, but not in the patient.

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: The patient had symptomatic juxtapapillary capillary retinal angioma with associated epiretinal membrane (ERM). Pars Plana Vitrectomy and removal of ERM resulted in substantial improvement of vision.

CaseNotHPOs: HP:0009713, HP:0000107( Spinal Hemangioblastoma, Renal Cyst)

CaseNotHPOFreeText: Magnetic resonance imaging revealed spinal hemangioblastomas and kidney cysts in the father, but not in the patient.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: (407C>G)

CaseProblemVariantFreeText: N/A

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

CAID: CA020099 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA020099

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 3

Case: Age, Sex, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Familial VHL

CasePresentingHPOs: HP:0009711; HP:0010797; HP:0001737; HP:0005584; HP:0000107 (retinal capillary hemangioma, hemangioblastoma, pancreatic cysts, renal cell carcinoma, renal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: Previously reported, HGMD (Human Gene Mutation Database: http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/120488.html)

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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: 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

GroupID: 53

DiseaseAssertion: assumed VHL

GroupSize: 8

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 8 of the 573 patients discussed in this paper were found to have identical variants. This mutation (S65W (c.194C>G)) was found in 1 VHL family with 8 patients.

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

GroupHPOFreeText: 6 had retinal hemangioblastoma, 5 had cerebellar hemangioblastomas, and 1 had renal cell carcinoma. Mean ages for each diagnosis follows: 32 (RH), 39 (CHB), 56 (RCC - with one patient)

GroupNotHPOs: HP:0002666 (pheochromcytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

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

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

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

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: 10

KindredID: 10

Case: M, 26Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009713 (spinal hemangioblastoma)

CaseHPOFreeText: The patient had a spinal hemangioblastoma at the C4/C5 boundary. The patient showed an high-normal Hb values (18.6) which fits the polyglobulia disease criteria. After the spinal hemangioblastoma was removed, the Hb normalized.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: p.S65W(c.407C>G)

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