Case1: 13 year old female

DiseaseAssertion: LVNC

FamilyInfo: No family history of cardiac disease

ParentalTesting:NR

CasePresentingHPOs: HP:0011664. HP:0002094. HP:0001279. HP:0031295

CaseHPOFreeText:Left Ventricular noncompaction, Dyspnea (shortness of breath), Fainting, Left atrial enlargement

CaseNotHPOs:HP:0000929. HP:0001712

CaseNotHPOFreeText:Abnormal skull morphology, left ventricular hypertrophy

CasePreviousTesting:

Genotyping Method:Next-Generation Sequencing (NGS)

FunctionalAnalysis:NR

Variant:c.575G>A

ClinVar:12424

CAID:CA021957

gnomAD:NR

AdditionalInfo:NR

Case1:19 Year-old male

DiseaseAssertion:HCM

FamilyInfo:None documented

ParentalTesting:

CasePresentingHPOs:HP:0001639

CaseHPOFreeText:Hypertrophic Cardiomyopathy

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting:

Genotyping Method:Next Generation Sequencing

FunctionalAnalysis:

Variant:c.442G>A, (p.Gly148Arg)

ClinVar:42752

CAID: CA015105

gnomAD:NR

AdditionalInfo:NR

Case1:Male, 46 years old

DiseaseAssertion:NR

FamilyInfo: 3 generations of asymptomatic carriers

ParentalTesting:NR

CasePresentingHPOs:NR

CaseHPOFreeText:

CaseNotHPOs:HP:0001712

CaseNotHPOFreeText:Left Ventricular hypertrophy

CasePreviousTesting:NR

Genotyping Method: NR

FunctionalAnalysis:

Variant: c.170C>A VUS

ClinVar:43121

CAID:CA013575

gnomAD: NR

AdditionalInfo:

All patients included in the study were VHL mutation carriers of 18 years or older examined between 1972 and 2012 in the VHL expertise centers University Medical Center Groningen (UMCG) and University Medical Center Utrecht (UMCU). Clinical data of 75 VHL mutation carriers were retrospectively retrieved from electronic and written patient record. Of these patients, one was found to harbour the c.462A>C germline mutation of the VHL gene. They presented with a cerebellar hemangioblastoma, renal cyst and pheochromocytoma. Their age at the last follow-up was 71. Previously published in: PMID 24132471.

PatientID: None

KindredID: 14

Case: Sex Unknown, 65Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: All VHL mutation carriers of 18 years or older who underwent surveillance according to Dutch VHL guidelines between 1972 and 2012 in the VHL expertise centers University Medical Center Groningen (UMCG) and University Medical Center Utrecht (UMCU) were included. Patients with VHL-disease subtype 2C (pheochromocytoma only) were excluded.

CasePresentingHPOs: HP:0009711; HP:0006880; HP:0009713; HP:0005584; HP:0030405; HP:0000107; HP:0001737; HP:0002666 (Retinal capillary hemangioma, Cerebellar hemangioblastoma, Spinal hemangioblastoma, Renal cell carcinoma, Pancreatic endocrine tumor, Renal cyst, Pancreatic cysts, Pheochromocytoma)

CaseHPOFreeText: VHL Type 2a/b.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 24132471

SupplementalData: Table 1

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

GroupID: 9

DiseaseAssertion: assumed VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 3 of the 573 patients discussed in this paper were found to the mutation belonging to 1 family. This mutation was found in 1 VHL family with 3 patients.

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

GroupHPOFreeText: 2 patients had retinal angiomas diagnosed at a mean age of 15Y, 2 patients had cerebellar hemangioblastomas diagnosed at a mean age of 15Y, and 1 patient had RCCs with an age of diagnosis of 40Y.

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.S72Pfs*87 (c.214del)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA658795180 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.214del

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: S72fs (c.214del)

MultipleGeneVariants: N/A

GroupID: 21

Case: Age unknown, Sex Unknown, Ethnicity Unknown

DiseaseAssertion: asymptomatic

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: Unknown

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.T124Mfs*33 (c.371_377delCACACGA)

LegacyVariant: p.T124Mfs*33 (c.369_375delGACACAC)

CaseProblemVariantFreeText: written in paper as:c.369_375del, automaps to NM_000551.3:c.371_377del - most up to date transcript

ClinVarID: N/A

CAID: CA913189240 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.371_377delCACACGA

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: G123fs (c.369_375delGACACAC)

MultipleGeneVariants: N/A

GroupID: 20

Case: 19Y0M, Sex Unknown, Ethnicity Unknown

DiseaseAssertion: retinal capillary hemangioma

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 (retinal capillary hemangioma)

CaseHPOFreeText: patient had retinal angiomas diagnosed at 19Y

CaseNotHPOs: HP:0005584; HP:0002666; HP:0006880 (renal cell carcinoma; pheochromocytoma; cerebellar hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.T124Hfs*35 (c.369delG)

LegacyVariant: p.Thr124Hisfs*35 (c.367delG)

CaseProblemVariantFreeText: c.367delG automaps to c.369delG - most up to date transcript

ClinVarID: N/A

CAID: CA432421810 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.369delG

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: T124fs (c.369del)

MultipleGeneVariants: N/A

GroupID: 2

DiseaseAssertion: cerebellar hemangioblastoma

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 identical variants. This mutation (c.162_163insT) was found in 1 VHL family with 2 patients.

GroupPresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

GroupHPOFreeText: both patients had cerebellar hemangioblastomas with a mean age of diagnosis of 19Y

GroupNotHPOs: HP:0005584; HP:0009711; HP:0002666 (renal cell carcinoma; retinal capillary hemangioma, pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.E55* (c.162_163insT)

CaseProblemVariantFreeText: The mutation was written as follows: AFO10238:375_376insT; NM_000551.2:c.162_163insT; p.54MetX. Author Maher was contacted and confirmed "A single nucleotide insertion (T) was detected at position 375 (375insT)” from 2000 lab report - June 1, 2021 - therefore assume p. was transcribed incorrectly.

LegacyVariant: p.54MetX (c.375_376insT)

ClinVarID: N/A

CAID: CA2499307063 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499307063

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: E55* (c.162_163insT)

MultipleGeneVariants: N/A

GroupID: 64

Case: 49Y0M, 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.340G>T) was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: patient had cerebellar hemangioblastoma diagnosed at 49Y

CaseNotHPOs: HP:0005584; HP:0009711; HP:0002666 (renal cell carcinoma; retinal capillary hemangioma; pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.G114C (c.340G>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA351751376 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.340G%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114C (c.340G>T)

MultipleGeneVariants: N/A

PatientID: 3

KindredID: 3

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: renal cell carcinoma

FamilyInfo: None

CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: deletion (deletion on chromosome 3 (>35kb, <90kb) resulting in complete loss of VHL gene)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: germline deletion on chromosome 3 (>35kb, <90kb) resulting in complete loss of VHL gene. Renal cell carcinoma sample from this patient shows a missense mutation R69C(c.205C>T) in the second copy of VHL gene.

MutationType: deletion

CivicName: Deletion AND R69C (c.205C>T)

MultipleGeneVariants: Somatic, VHL, c.205C>T (p.Arg69Cys)

GroupID/ KindredID: 26

PatientID: I

Case: 37Y0M, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: Family 26 consisted of 2 members; One other member (40Y) was diagnosed with a single spinal HAB, and a single cerebellar HAB at 38Y.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Patient was diagnosed with a single cerebellar HAB at 32Y

CaseNotHPOs: HP:0009711; HP:0005584; HP:0009713 (retinal capillary hemangioma; renal cell carcinoma; spinal hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: complete deletion of VHL gene

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Haplotype analysis information in Table 3

MutationType: deletion

CivicName: deletion

MultipleGeneVariants: N/A

GroupID/ KindredID: 22 / S 4

Case: Age unknown, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: This deletion was found in Family No. 22 with 1 member affected. Germline de novo mutations confirmed by analysis of parents’ DNA. Germline mutations (of deletion of exon 2-3) was not detected in DNA extracted from blood leucocytes of the parents.

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exons 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

GroupID/ KindredID: 13

DiseaseAssertion: VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Polish

GroupAgeRange: N/A

GroupInfo: Familial VHL stated; 3 family members recorded with this mutation.

GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0005584 (retinal capillary hemangioma, hemangioblastoma; renal cell carcinoma)

GroupHPOFreeText: All 3 patients were tallied with a retinal capillary hemangiomas, 2 with cHemangioblastomas, and 1 with RCC. These phenotypes couldn’t be paired as it was not clear with each member.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.A149Pfs*10 (c.445delG)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA432421902 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.445delG

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: A149fs (c.445delG)

MultipleGeneVariants: N/A

GroupID/ KindredID: 17

Case: Age unknown, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: This mutation (R167Q (c.500G>A)) was found in Family No. 17 with 1 member affected.

CasePresentingHPOs: HP:0009711; HP:0002666 (retinal capillary hemangioma, pheochromcytoma)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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: 347

KindredID: 347

Case: Sex Unknown, 30Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history is positive but no details provided.

CasePresentingHPOs: HP:0010797; HP:0000107 (Hemangioblastoma, Renal cyst)

CaseHPOFreeText: CNS hemangioblastoma and renal cyst.

CaseNotHPOs: HP:0002666; HP:0006770; HP:0009711; HP:0001732 (Pheochromocytoma, Clear cell renal cell carcinoma, Retinal capillary hemangioma, Abnormality of the pancreas)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished:N/A

SupplementalData: Table S1, S2 and S3

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; deletion

CivicName: Exon 1 Deletion

MultipleGeneVariants: N/A

PatientID: 422

KindredID: 422

Case: Sex Unknown, 49Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma.

CaseNotHPOs: HP:0009711; HP:0006770; HP:0002666; HP:0001732; HP:0000107 (Retinal capillary hemangioma, Clear cell renal cell carcinoma, Pheochromocytoma, Abnormality of the pancreas, Renal cyst)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17024664

SupplementalData: Table S1, S2 and S3

Variant: p.L135Yfs*24 (c.404del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432421852, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.404del

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion; minus_1_frameshift_variant

CivicName: L135fs (c.404del)

MultipleGeneVariants: N/A

PatientID: 221

KindredID: 221

Case: Sex Unknown, 16Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0010797; HP:0006770; HP:0002666; HP:0000107; HP:0001732 (Hemangioblastoma, Clear cell renal cell carcinoma, Pheochromocytoma, Renal cyst, Abnormality of the pancreas)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17006605

SupplementalData: Table S1, S2 and S3

Variant: c.-61_-51dup

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 517152, https://www.ncbi.nlm.nih.gov/clinvar/variation/517152/

CAID: N/A

gnomAD: 0.00009581, https://gnomad.broadinstitute.org/variant/3-10183466-C-CTCCGCCCCGCG?dataset=gnomad_r2_1

VariantEvidence: Variant was reported as c.-65_-55dup11 which was mapped to c.-61_-51dup.

MutationType: splice_site_variant; duplication; plus_2_frameshift_variant; 5_prime_UTR_variant

CivicName: c.-61_-51dup11

MultipleGeneVariants: N/A

PatientID: 398

KindredID: 398

Case: Sex Unknown, 28Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: CNS hemangioblastoma and pancreatic cyst or tumor.

CaseNotHPOs: HP:0002666; HP:0006770; HP:0000107; HP:0009711 (Pheochromocytoma, Clear cell renal cell carcinoma, Renal cyst, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished:N/A

SupplementalData: Table S1, S2 and S3

Variant: Exon 2 Deletion (c.341-?_463+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant; deletion

CivicName: Exon 2 Deletion

MultipleGeneVariants: N/A

In a study of 426 unrelated VHL patients, 111 were discovered to have alterations in the VHL gene. 18 novel variants were identified in VHL patients, but none were present in 200 unaffected control individuals. DNA samples from peripheral blood leukocytes underwent polymerase chain reaction (PCR) amplification, denaturing high-performance liquid chromatography (DHPLC), and direct sequence analysis of the entire coding sequence and intron-exon boundaries. The V155G (c.464T>G) germline mutation of the VHL gene was found in a 43 yr old VHL patient with retinal hemangioblastomas and pheochromocytoma (index case 2). Parents, siblings and nephew were negative for the mutation confirming that this variant was de novo in the proband. No phenotype details are noted for these family members.

In a study of 426 unrelated VHL patients, 111 were discovered to have alterations in the VHL gene. 18 novel variants were identified in VHL patients, but none were present in 200 unaffected control individuals. DNA samples from peripheral blood leukocytes underwent polymerase chain reaction (PCR) amplification, denaturing high-performance liquid chromatography (DHPLC), and direct sequence analysis of the entire coding sequence and intron-exon boundaries. The N141Ifs*12 (c.422_440del) germline variant of the VHL gene was found in a 23 year old patient (ID 80) presenting with CNS hemangioblastoma and renal cystic lesion. Parents were negative for the mutation, confirming it as de novo in the proband. No phenotype details are noted for these family members.

PatientID: 223

KindredID: 223

Case: Sex Unknown, 35Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Positive family history for VHL.

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

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0001737, HP:0002666, HP:0006770, HP:0009711 (pancreatic cysts, 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.R167Q(c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 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

PatientID: 7

KindredID: 7

Case: Sex Unknown, 51Y0M, Ethnicity Unknown

DiseaseAssertion: clear cell renal cell carcinoma

FamilyInfo: N/A - not stated

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

CaseHPOFreeText: Bilateral clear cell RCC was first diagnosed between 49-51Y of age

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes

Variant: c.340+578C>T

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 849869 https://www.ncbi.nlm.nih.gov/clinvar/variation/849869/

CAID: N/A

gnomAD: 0.0005097 https://gnomad.broadinstitute.org/variant/3-10184449-C-T

VariantEvidence: N/A

MutationType: splice_site_variant; intron_variant

CivicName: Splice Site (c.340+578C>T)

MultipleGeneVariants: N/A

PatientID: 26

KindredID: 26

Case: F, 46Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: Family history positive for VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

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

CaseHPOFreeText: CNS hemangioblastomas. Diagnosed with VHL Type 2B.

CaseNotHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V87A (c.260T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: coding DNA and protein position (c.341T>C, p.Val114Arg) do not match reference sequence. “We found our error of changing the nucleotide code "A" to the three-letter code "Arg", which should be corrected to "ALA" based on the reference NM_001354723.1(VHL). It could be corrected as follows; NM_000551.3(VHL): c.260T>C (p.Val87Ala).” (Author Rhee comment)

ClinVarID: N/A

CAID: CA351750654, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA351750654

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: V87A (c.260T>C)

MultipleGeneVariants: N/A

PatientID: 33

KindredID: 33

Case: M, 33Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797; HP:0005584 (Hemangioblastoma, Renal cell carcinoma)

CaseHPOFreeText: Multiple or bilateral CNS hemangioblastomas and renal cell carcinoma. Other phenotypes presented but not specified (one or more of: pancreatic cyst or tumor, renal or hepatic cyst). Diagnosed with VHL Type 1.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L140Sfs*4 (c.417dup)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2573051216, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA2573051216

gnomAD: N/A

VariantEvidence: Stated as c.417_418insT by the authors.

MutationType: duplication; plus_1_frameshift_variant

CivicName: L140Sfs*4 (c.417dup)

MultipleGeneVariants: N/A

PatientID: 53

KindredID: 53

Case: M, 36Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: Family history positive for VHL. No further details provided.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797; HP:0005584 (Hemangioblastoma, Renal cell carcinoma)

CaseHPOFreeText: CNS hemangioblastoma. Other phenotypes presented but not specified (one or more of: pancreatic cyst or tumor, renal or hepatic cyst). Diagnosed with VHL Type 1.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19270817

SupplementalData: N/A

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: 5

KindredID: 5

Case: M, 43Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797; HP:0005562 (Hemangioblastoma, Multiple renal cysts)

CaseHPOFreeText: Multiple or bilateral CNS hemangioblastoma and renal cysts. Diagnosed with VHL Type 1. Phenotypes revised from previous reports (see “PreviouslyPublished” section below for PMID).

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19270817 and/or 19949673

SupplementalData: N/A

Variant: p.E70K (c.208G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43598, https://www.ncbi.nlm.nih.gov/clinvar/variation/43598/

CAID: N/A

gnomAD: 0.000004365, https://gnomad.broadinstitute.org/variant/3-10183739-G-A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: E70K (c.208G>A)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 42

Case: Age, sex ethnicity unknown

DiseaseAssertion: unknown; paper focused only on pheochromocytoma

FamilyInfo: No specific family info was present; although this was recorded as a family germline mutation belonging to Family ID 42

CasePresentingHPOs: N/A

CaseHPOFreeText: Unknown

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: No presence of phaeochromocytoma in family

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.C162Y (c.485G>A)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.C162Y (c.698G>A)

ClinVarID: 223225 https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: C162Y (c.485G>A)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 113

Case: Age, sex ethnicity unknown

DiseaseAssertion: unknown; paper focused only on pheochromocytoma

FamilyInfo: No specific family info was present; although this was recorded as a family germline mutation belonging to Family ID 113

CasePresentingHPOs: Unknown

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: No presence of phaeochromocytoma in family

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L188Rfs*14 (c.563delT)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.L188fs (c.776delT)

ClinVarID: N/A

CAID: CA432423679 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.563delT

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: L188fs (c.563delT)

MultipleGeneVariants: N/A

PatientID: 8

KindredID: Unknown

Case: F, 28Y0M, Dutch

DiseaseAssertion: VHL

FamilyInfo: Unknown - study sampled 15 patients from 5 families

CasePresentingHPOs: HP:0001737; HP:0009711 (pancreatic cyst, retinal capillary hemangioma)

CaseHPOFreeText: retinal capillary hemangioma of the right eye

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V170D (c.509T>A)

LegacyVariant: p.V241D

CaseProblemVariantFreeText: Variant determined through the assumption of the authors using Latif et al 1993 (AF010238.1) transcript and adding 71bp to the protein sequence.

ClinVarID: 625256 https://www.ncbi.nlm.nih.gov/clinvar/variation/625256/

CAID: N/A

gnomAD: N/A

VariantEvidence:N/A

MutationType: missense_variant;transversion

CivicName: V170D (c.509T>A)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: Unknown

Case: M, 38Y0M, Dutch

DiseaseAssertion: VHL

FamilyInfo: Unknown - study sampled 15 patients from 5 families

CasePresentingHPOs: HP:0001737; HP:0009711; HP:0006880; HP:0009713; HP:0000107; HP:0006706 (pancreatic cyst, retinal capillary hemangioma, cerebellar hemangioblastoma, spinal hemangioblastoma, renal cyst, cystic liver disease)

CaseHPOFreeText: retinal capillary hemangioma of the right eyes, pancreatic, renal and liver cysts (cystic liver disease), and cerebellar and spinal hemangioblastoma

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V170D (c.509T>A)

LegacyVariant: p.V241D

CaseProblemVariantFreeText: Variant determined through the assumption of the authors using Latif et al 1993 (AF010238.1) transcript and adding 71bp to the protein sequence.

ClinVarID: 625256 https://www.ncbi.nlm.nih.gov/clinvar/variation/625256/

CAID: N/A

gnomAD: N/A

VariantEvidence:N/A

MutationType: missense_variant;transversion

CivicName: V170D (c.509T>A)

MultipleGeneVariants: N/A

PatientID: 10

KindredID: Unknown

Case: M, 40Y0M, Dutch

DiseaseAssertion: VHL

FamilyInfo: Unknown - study sampled 15 patients from 5 families

CasePresentingHPOs: HP:0001737; HP:0000107; HP:0010797; HP:0006880; HP:0005584 (pancreatic cysts, renal cyst, cerebellar hemangioblastoma, spinal hemangioblastoma, renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0009711 (retinal capillary hemangioma)

CaseNotHPOFreeText: No evidence of left or right eye angiomas

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: p.R238Q

CaseProblemVariantFreeText: Variant determined through the assumption of the authors using Latif et al 1993 (AF010238.1) transcript and adding 71bp to the protein sequence.

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: 49

KindredID: N/A

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: The authors evaluated 64 VHL patients (32 women and 32 men) with renal involvement of whom 54/64 had undergone renal surgery or a radiofrequency thermal ablation procedure for RCC. In 10/64 VHL patients, at least one or more RCC were diagnosed, however at the time of diagnosis an indication for treatment was not yet present. For all patients several CT/MRI scans existed for retrospective description of tumour growth kinetics.

CasePresentingHPOs: HP:0005584 (Renal cell carcinoma)

CaseHPOFreeText: This is a tumor resolution study (VHL patients were investigated based on the presence of renal tumors.) No other phenotypic information is available.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S5 describes 8 patients with small deletions, including this patient.

Variant: p.R177Dfs*25 (c.528del)

LegacyVariant: c.740delG

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432423454

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant; deletion

CivicName: R177fs(c.528del)

MultipleGeneVariants: N/A

PatientID: 15

KindredID: N/A

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: The authors evaluated 64 VHL patients (32 women and 32 men) with renal involvement of whom 54/64 had undergone renal surgery or a radiofrequency thermal ablation procedure for RCC. In 10/64 VHL patients, at least one or more RCC were diagnosed, however at the time of diagnosis an indication for treatment was not yet present. For all patients several CT/MRI scans existed for retrospective description of tumour growth kinetics.

CasePresentingHPOs: HP:0005584 (Renal cell carcinoma)

CaseHPOFreeText: This is a tumor resolution study (VHL patients were investigated based on the presence of renal tumors.) No other phenotypic information is available.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S5 describes 8 patients with small deletions, including this patient.

Variant: p.L129Wfs*30 (c.384del)

LegacyVariant: c.597delT (p.128fs)

CaseProblemVariantFreeText: Submitted revision on CIViC for correct CIViC name: L129Wfs*30 (c.384del).

ClinVarID: N/A

CAID: CA70049452

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant; deletion

CivicName: L129Wfs*?(c.383delT)

MultipleGeneVariants: N/A

GroupID/ KindredID: VHL 57

Case: Sex unknown, Age unknown, German

DiseaseAssertion: assumed VHL

FamilyInfo: One patient with the given mutation is stated to belong to VHL family 57

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.464-2A>T

CaseProblemVariantFreeText: N/A

LegacyVariant: c.677-2A>T

ClinVarID: N/A

CAID: CA70052157 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.464-2A%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: Splice Site (c.464-2A>T)

MultipleGeneVariants: N/A

GroupID: None

Case: Sex Unknown, 71Y0M, Dutch

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0006880; HP:0002666; HP:0000107 (Cerebellar hemangioblastoma, Pheochromocytoma, Renal cyst)

CaseHPOFreeText: This individual was classified as 2a/b meaning that it included de novo VHL mutation carriers or VHL mutation carriers having a family history with diagnosis of pheochromocytoma and other VHL related manifestations.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 31087189

SupplementalData: N/A

Variant: p.P154= (c.462A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA16621934, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.462A%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion; synonymous_variant

CivicName: P154= (c.462A>C)

MultipleGeneVariants: N/A

GroupID: None

Case: Sex Unknown, 42Y0M, Dutch

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711; HP:0006880; HP:0009713; HP:0005584; HP:0000107; HP:0001737 (Retinal capillary hemangioma, Cerebellar hemangioblastoma, Spinal hemangioblastoma, Renal cell carcinoma, Renal cyst, Pancreatic cysts)

CaseHPOFreeText: Diagnosed with VHL Type 1.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 31087189

SupplementalData: N/A

Variant: p.V87Dfs*45 (c.259_260insA)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA913189242, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA913189242

gnomAD: N/A

VariantEvidence: N/A

MutationType: insertion; plus_1_frameshift_variant

CivicName: V87fs (c.259_260insA)

MultipleGeneVariants: N/A

PatientID: 18

KindredID: 355

Case: Sex unknown, Age unknown, French

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666; HP:0030405 (pheochromocytoma, pancreatic endocrine tumour)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584 (renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: NONE (unspecified large rearrangement)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence:N/A

MutationType: rearrangement_region

CivicName: rearrangement

MultipleGeneVariants: N/A

PatientID: 3

KindredID: 76

Case: Sex unknown, Age unknown, French

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666; HP:0030405; HP:0005584 (pheochromocytoma, pancreatic endocrine tumour, renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: NONE (unspecified large rearrangement)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence:N/A

MutationType: rearrangement_region

CivicName: rearrangement

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 40

Case: Sex unknown, Age unknown, French

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666; HP:0030405; HP:0005584 (pheochromocytoma, pancreatic endocrine tumour, renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: NONE (unspecified large rearrangement)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence:N/A

MutationType: rearrangement_region

CivicName: rearrangement

MultipleGeneVariants: N/A

Among patients prospectively followed by the members of the French VHL Study Group, 35 consecutive patients with well-documented endocrine pancreatic tumour (20 women and 15 men; median age,37 [21Y-57] years) were included. The data from 7 patients with EPT have been partially reported previously in Hammel et al., 1995;2000. All 35 patients had VHL germline mutations and were assessed for the presence of pheochromocytoma and renal carcinoma in addition to pancreatic tumours. The presence of other phenotypes was not described. A germline nonsense mutation (c.525C>A) was found in patient no. 35 from family 7, presenting with pancreatic endocrine tumour. No family history was discussed.

GroupID: None

DiseaseAssertion: VHL

GroupSize: 35

GroupNumberMales: 23

GroupNumberFemales: 12

GroupEthnicity: Chinese

GroupAgeRange: N/A

GroupInfo: 13 families (35 patients total, 33 of which are alive) in the partial deletion group had a CNS hemangioblastoma (see table 1)

GroupPresentingHPOs: HP:0010797 (Hemangioblastoma

GroupHPOFreeText: N/A

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 32432044 (Potential overlap, same authors)

SupplementalData:  N/A

Variant: Partial Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion

CivicName: Null (Partial Deletion)

MultipleGeneVariants: N/A

PatientID: II

KindredID: 19

Case: Sex Unknown, 1Y0M, Danish

DiseaseAssertion: Asymptomatic

FamilyInfo: 3 other family members presented with this VHL variant. Patients 19-I and 19-III were asymptomatic. Patient 19-IV presented with 2 retinal hemangioblastomas (10Y and 12Y) and kidney disease (17Y).

CasePresentingHPOs: N/A

CaseHPOFreeText: Diagnosed with VHL at age 0Y. Age at the end of study: 1Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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: Null (c.464-?_642+?del)

MultipleGeneVariants: N/A

PatientID: II

KindredID: 2

Case: Sex Unknown, 5Y0M, Danish

DiseaseAssertion: Asymptomatic

FamilyInfo: One other family member presented with his VHL mutation and was asymptomatic.

CasePresentingHPOs: N/A

CaseHPOFreeText: Diagnosed with VHL at age 4Y. Age at the end of study: 5Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V130I (c.388G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753916, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.388G%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: V130I (c.388G>A)

MultipleGeneVariants: N/A

PatientID: 10

KindredID: 10

Case: M, 7Y0M, Ethnicity Unknown

DiseaseAssertion: paraganglioma

FamilyInfo: No details on family information provided.

CasePresentingHPOs: HP:0002668 (paraganglioma)

CaseHPOFreeText: Patient had mediastinum paraganglioma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.D126N (c.376G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 141044, https://www.ncbi.nlm.nih.gov/clinvar/variation/141044/

CAID: N/A

gnomAD: 0.00001988, https://gnomad.broadinstitute.org/variant/3-10188233-G-A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: D126N (c.376G>A)

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: 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

A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were included for analysis. This mutation was confirmed in kindred 56. A male proband, patient 154, presented with a retinal angioma, renal cell carcinoma, and multiple pancreatic cysts/tumors at age 34. No family information was given. This kindred was also published in an earlier paper by Wang et al., 2014 (PMID 24581539) as well as a later paper by Wang et al., 2018 (PMID: 29330336).

PatientID: 59

KindredID: 22

Case: M, 14Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666; HP:0001732; HP:0001737 (Pheochromocytoma, Abnormality of the pancreas, Pancreatic cysts)

CaseHPOFreeText: The proband presented with multiple pancreatic cysts/tumors at 14 and pheochromocytoma at 11.

CaseNotHPOs: HP:0010797; HP:0009711; HP:0005584 (Hemangioblastoma, Retinal capillary hemangioma, 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.V87E (c.260T>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351750651; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.260T%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: V87E (c.260T>A)

MultipleGeneVariants: N/A

PatientID: 154

KindredID: 57

Case: M, 34Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

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 34 with retinal angioma, 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 an earlier paper by Wang et al., 2014 (PMID 24581539) as well as a later paper by Wang et al., 2018 (PMID: 29330336).

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

Variant: p.V155Dfs*17 (c.464_468del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2499306942; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499306942

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_2_frameshift_variant

CivicName: V155fs (c.464_468delTGTAT)

MultipleGeneVariants: N/A

PatientID: 123

KindredID: 43

Case: M, Age 60Y0M, Chinese

DiseaseAssertion: VHL

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

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

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

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

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

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

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

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

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117R (c.349T>A)

MultipleGeneVariants: N/AcDNAposition:349

A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were included for analysis. An in-frame deletion (c.227_229del, equivalent to c.224_226del) was confirmed in 3 families (#9, #10 and #11). Family #9: A female patient (patient #27) was confirmed for this in-frame deletion in the VHL gene. She was diagnosed with CNS haemangioblastoma at 36Y, renal cell carcinoma at 40Y, and multiple pancreatic cysts or tumours at 40Y. Family #10: A male patient (#28) was diagnosed with CNS hemangioblastoma at 21Y and confirmed to have the mutation. His son (#29) was also confirmed to have the mutation, but was asymptomatic (age unknown). Family #11: A female proband (#30) was diagnosed with CNS hemangioblastoma at 28Y, retinal angioma at 26Y, renal cell carcinoma at 37Y, and multiple pancreatic cysts or tumours at 28Y (mutation confirmed); her son (#31) with a mutation confirmed but no manifestations (asymptomatic) and age unknown. She had four family members who passed away before they could be confirmed with the mutation. Her father (#32) diagnosed with CNS hemangioblastoma at 42Y; Brother 1 (#32) diagnosed with CNS hemangioblastoma at 28Y; Brother 2 (#33) diagnosed with CNS hemangioblastoma at 30Y; and uncle (#34) with retinal angioma diagnosed at 60Y. This cohort was also published in a paper by Wang et al., 2018 (PMID: 29330336). This mutation was also published in PMID 32179488 in reference to one patient with VHL disease type 1 in this paper with the c.227_229del variant. However, it is unclear whether patient #27, #28, or #30 is specifically published in PMID 32179488.

A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were included for analysis. This familial mutation was confirmed in family #58 with 3 affected members who were all genetically confirmed with the mutation. A male proband (patient 155) was diagnosed with retinal angioma at 21Y, renal cell carcinoma at 26Y, and multiple pancreatic cysts/tumors at 26Y. His sister (patient 156) was diagnosed with CNS hemangioblastoma at 21Y and multiple pancreatic cysts/tumors at 27Y. His nephew (son of sister) of unknown age was asymptomatic at the time of analysis. This kindred was also published in a paper by Wang et al., 2018 (PMID: 29330336).

PatientID: 25

KindredID: 7

Case: M, 58Y0M, 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:0001737; HP:0001732; HP:0005584 (Pancreatic cysts, Abnormality of the pancreas, Renal cell carcinoma)

CaseHPOFreeText: The proband's father, patient 25, presented with renal cell carcinoma and multiple pancreatic cysts/tumors.

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

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

GroupID: 8

DiseaseAssertion: Neuroendocrine neoplasm (pheochromocytoma or paraganglioma)

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Ethnicity unknown

GroupAgeRange: N/A

GroupInfo: This mutation (p.R161Q (c.482G>A)) was found in 3 patients, 1 with a family history and/or a syndromic presentation, and 2 patients with an apparently sporadic presentation.

GroupPresentingHPOs: HP:0100634 (Neuroendocrine neoplasm)

GroupHPOFreeText: Patients with a pheochromocytoma or a functional paraganglioma were recruited from several different French clinical centers participating in several clinical research networks (Cortico et Medullosurrènale: les Tumeurs Endocrines, Paragan-Glioma Network, Groupe des Tumeurs Endocrines)

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R161Q (c.482G>A)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 182983 https://www.ncbi.nlm.nih.gov/clinvar/variation/182983/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R161Q (c.482G>A)

MultipleGeneVariants: N/A

GroupID: 183

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: VHL family found to have a germline rearrangement of the VHL gene. The number of family members included in this study is not specified. Likely previously published in PMID 32179488 (Kindred 14) but correspondence to a patient in this group is not confirmed.

GroupPresentingHPOs: N/A

GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease, however, the presenting phenotypes were not specified.

GroupNotHPOs: HP:0002666 (Pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: Stated as being previously reported in PMID 7728151 (2 families reported with this mutation) and/or 8956040 (7 families reported with this mutation). Likel

SupplementalData: N/A

Variant: p.F76del (c.227_229del)

LegacyVariant: c.439_441delTTC

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA357012, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.226_228del

gnomAD: N/A

VariantEvidence: NM_000551.3:c.226_228delTTC automaps to NM_000551.3:c.227_229delTCT due to redundancy

MutationType: deletion; inframe_deletion

CivicName: F76del (c.227_229del)

MultipleGeneVariants: N/A

93 families examined at the Clinical Center of the National Institutes of Health (Bethesda, MD) underwent genetic testing for germline mutations of the VHL gene. Whole blood was extracted and genomic DNA was amplified by PCR and products were sequences using a cycle sequencing kit with dye-labeled terminators and automatically sequenced. This mutation was found in VHL type 1 family (lineage 11). The variant was reported as c.488_490del18bp (AF010238.1) and was mapped to G93_Y98del (c.277_294del/c.275_292del) (NM_000551.3).

PatientID: VHL-12

KindredID: 12

Case: Sex Unknown, Age Unknown, Italian

DiseaseAssertion: VHL

FamilyInfo: Family history of VHL. No further details provided.

CohortInfo: Forty-three index cases were referred to the Service of Medical Genetics, Genova, for germline mutation analysis in the VHL gene between 1995 and 2008.

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

CaseHPOFreeText: Multiple CNS hemangioblastomas. Clinical classification: A1.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.I109Tfs*50 (c.326del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA658820709, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.326del

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant; deletion

CivicName: I109TfsX50 (c.326del)

MultipleGeneVariants: N/A

PatientID: N/A (Case 3)

KindredID: 1

Case: Sex Unknown, 16Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Patient’s two younger 9Y0M twin siblings possessed the same VHL variant and had abnormal vestibular assessments.

CasePresentingHPOs: HP:0001756 (Vestibular hypofunction)

CaseHPOFreeText: Following a genetic VHL diagnosis, patient presented with no audiovestibular symptoms. Vestibular assessment highlighted covert saccades in the left posterior semicircular canal on vHIT. Patient also showed signidicant assymmetry with weakness on the right side.

CaseNotHPOs: HP:0009713; HP:0006880 (spinal hemangioblastoma; cerebellar hemangioblastoma)

CaseNotHPOFreeText: peripheral hearing assessment and screening MRI of brain/spine were normal.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 1-3 Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion

CivicName: Exon 1-3 Deletion

MultipleGeneVariants: N/A

PatientID: 6

KindredID: 6

Case: F, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0000107; HP:0005584; HP:0010797; HP:0001737; HP:0009711 (Renal cyst, Renal cell carcinoma, Hemangioblastoma, Pancreatic cysts, Retinal capillary hemangioma)

CaseHPOFreeText: Bilateral RCC add renal cysts, CNS hemangioblastoma, positive for pancreatic cysts, retinal hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: 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: The variant was noted as “c.464-?_642+?” by the authors; this was assumed to be a deletion. This study found coexpression of Epo and EpoR in 11 RCCs and in 10 benign renal cysts in a spectrum of VHL renal disease suggesting that Epo/EpoR coexpression is present in both benign and malignant stages of renal neoplasia. Six benign cysts stained for Epo but not EpoR. The researchers detected loss of heterozygosity of a wild-type VHL allele in different RCCs with microsatellite markers, D3S1110 and D3S2452, flanking the VHL gene

MutationType: exon_loss_variant

CivicName: Exon 3 Deletion

MultipleGeneVariants: N/A

PatientID: III-4

KindredID: 2

Case: F, 48Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient’s 23Y daughter was diagnosed with VHL disease and spinal cord hemangioblastomas at 15Y. At 20Y, she had multiple cystic lesions in the right kidney, a solid lesion of the left kidney, multiple pancreatic cysts, and a small peripheral retinal angioma. She was also found to carry the same NM_000551.3:c.227_229del mutation the patient carried. The patient’s daughter’s mother was unaffected. Of the patient’s three other daughters and two brothers, one underwent clinical examination and two underwent genetic testing of unclear nature, and were found to be unaffected. The remaining two children of the patient were not evaluated.

CasePresentingHPOs: HP:0006880; HP:0001737; HP:0000107; HP:0006770 (Cerebellar hemangioblastoma, pancreatic cyst, renal cyst, clear cell renal cell carcinoma)

CaseHPOFreeText: The age 48Y patient originally presented with hematuria at age 39Y, and further investigation found clear-cell renal-cell carcinoma, renal cysts, pancreatic cysts, and multiple hemangioblastomas of the cerebellum and lower brainstem. Initial southern blot analysis and DNA sequencing of the VHL gene in the patient’s peripheral blood lymphocytes were negative; however, application of additional methods directed specifically at the region of the mutation found in the patient’s daughter (IV-6) discovered that approximately one-seventh of the patient’s peripheral blood lymphocytes carried the same VHL mutation the patient’s daughter carried, suggesting mosaic VHL disease.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F76del(c.226_228delTTC)

LegacyVariant: p.F76del(c.439_441delTTC)

ClinVarID: N/A

CAID: CA357012

gnomAD: N/A

VariantEvidence: Southern blot analysis and DNA sequencing of the VHL gene in the father's PBLs were negative (fig. 4A) by the initial genetic testing, on the basis of standard methods that identified VHL mutations in 99 of 99 (Stolle et al. 1998) and in a subsequent total of 131 of 131 (Glenn et al. 1999) affected individuals. However, genetic testing of the daughter's (IV:6) PBLs by direct sequencing revealed a 3-bp deletion (TTC) at nucleotides 439–441 (fig. 4B). After identification of the mutation in IV:6, the father's DNA was again analyzed, by application of additional methods directed specifically at the region of the 3-bp deletion

MutationType: inframe_deletion

CivicName: F76del(c.226_228delTTC)

MultipleGeneVariants: N/A

PatientID: 53 (Cousin)

KindredID: 18

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

CaseHPOFreeText: This patient presented with CNS hemangioblastoma (23Y) and retinal angioma (14Y).

CaseNotHPOs: HP:0005584; HP:0000077; HP:0001732; HP:0002666 (Renal cell carcinoma, Abnormality of the kidney, Abnormality of the pancreas, Pheochromocytoma)

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 (Proband)

KindredID: 13

Case: F, 15Y0M, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: 5 members of this family were found to harbour the deletion of one VHL allele. The sister (ID 2) and uncle (ID 5) were all asymptomatic. The father (ID 3) presented with CNS hemangioblastoma (34Y). The Grandmother (ID 9) presented with CNS hemangioblastoma (57Y).

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666; HP:0005584; HP:0009711; HP:0000077; HP:0001732; HP:0010797 (Pheochromocytoma, Renal cell carcinoma, Retinal capillary hemangioma, Abnormality of the kidney, Abnormality of the pancreas, Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Reported as “del one vHL allele”.

MutationType: deletion

CivicName: Null (del one VHL allele)

MultipleGeneVariants: N/A

PatientID: None (Twin)

KindredID: A-V6

Case: Sex Unknown, 30Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: 2 affected individuals (twin brothers) in this family.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Bilateral pheochromocytoma. Died of VHL.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 25078357

SupplementalData: N/A

Variant: N/A

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Family and medical history make it likely that this patient had the p.R167W (c.499C>T) germline variant of VHL (as did this patient's twin brother) but this was not genetically confirmed. The variant is reported in Table 1 as c.499G>T which was assumed to be a typo and was corrected to c.499C>T.

MutationType: N/A

CivicName: N/A

MultipleGeneVariants: N/A

PatientID: 4

KindredID: 4

Case: M, 30Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Strong family history of cerebellar hemangioblastoma.

CasePresentingHPOs: HP:0006880, HP:0030405, HP:0002666, HP:0001737 (cerebellar hemangioblastoma, pancreatic endocrine tumour, pheochromocytoma, pancreatic cysts)

CaseHPOFreeText: At age 26 was diagnosed with cerebellar hemangioblastoma. Four years later, he was found to have pancreatic endocrine tumour, pheochromocytoma, and pancreatic cysts.

CaseNotHPOs: HP:0005584 (Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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: None

KindredID: 1

Case: F, 0Y0M, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: The patient’s mother had bilateral adrenal pheochromocytoma at 27Y, and was found to have bilateral small lesions suspicious for inactive retinal angiomas upon further investigation. The patient’s grandfather had a right adrenal pheochromocytoma at 48Y, and was found to have left epididymal cysts and bilateral renal cysts upon further investigation. Genetic testing found that the patient’s mother and grandfather both carried the same NM_000551.3:c.277G>A mutation that the patient was found to carry. The patient's mother’s paternal grandmother had also died at 42Y as a result of a stroke, and the patient’s mother’s paternal grandmother’s brother had died at 57Y as a result of a stroke. There is no genetic information available about them. The patient’s aunt did not carry the mutation.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93S (c.277G>A)

LegacyVariant: N/A

ClinVarID: 2237, https://www.ncbi.nlm.nih.gov/clinvar/variation/2237/

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: G93S(c.277G>A)

MultipleGeneVariants: N/A

PatientID: V287

KindredID: V287

Case: Sex Unknown, Age Unknown, French

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Diagnosed with VHL Type 1.

CaseNotHPOs: HP:0002666 (Pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N67_V74del (c.198_221del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA645524685, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.198_221del

gnomAD: N/A

VariantEvidence: Variant was reported as c.197del24 which was mapped to c.198_221del.

MutationType: inframe_deletion; deletion

CivicName: N67_V74del (c.198_221del)

MultipleGeneVariants: N/A

Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found in 96 control cases. Direct sequencing on peripheral blood was systematically performed on exon 1 PCR products. Southern blotting was used to search for larger alterations to the gene. The P71Lfs*61 (c.211_212insT) mutation was found in a VHL type 1 (no pheochromocytoma) patient (patient no. V96).

PatientID: II-3

KindredID: I

Case: M, Age Unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: In the patient’s 12 member Chinese family, 7 members were found to carry the NM_000551.3:c.114delC mutation. Five had manifestations of CNS hemangioblastoma, and three of the five were deceased. The other two members found to carry the mutation were asymptomatic, although the paper states that this is likely due to their young age.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: The patient is deceased. The paper implies that the mutation was confirmed through stored tumour tissue.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G39Afs*28(c.114delC)

LegacyVariant: p.G39Afs*28(c.327delC)

ClinVarID: N/A

CAID: CA2573047816, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA2573047816

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: G39Afs(c.114delC)

MultipleGeneVariants: N/A

PatientID: IV-18

KindredID: 1

Case: F, 17Y0M, 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; HP:0009711 (Pheochromocytoma, retinal capillary hemangioma)

CaseHPOFreeText: Patient had a bilateral PCC and retinal HB at 14Y which was surgically removed at the time. Histopathology was benign, and there was no case of relapse or metastatic dissemination.

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: 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

A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot analysis of peripheral blood samples. The C77Sfs*82 (c.230del) germline mutation was found in a VHL type 1 patient with hemangioblastomas of the central nervous system and renal cell carcinoma (family ID 16). This individual was previously reported in PMID 8634692.

A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot analysis of peripheral blood samples. The F76del (c.227_229del) germline mutation was found in 2 VHL type 1 patients, both presenting with hemangioblastomas of the central nervous system, pancreatic cyst or tumor, and renal cell carcinoma (families ID 80 and 2). The variant was reported as c.437_439del and mapped to c.224_226del which is equivalent to c.227_229del. This family was previously reported in PMID 8634692.

PatientID: None

KindredID: 104

Case: Sex Unknown, Age Unknown, Japanese

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: Pheochromocytoma, renal cell carcinoma, pancreatic cyst or tumor (unspecified) and retinal angioma.

CaseNotHPOs: HP:0010797 (Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.C162Y (c.485G>A)

LegacyVariant: c.698G>A

CaseProblemVariantFreeText: N/A

ClinVarID: 223225, https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: C162Y (c.485G>A)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 48

Case: Sex Unknown, Age Unknown, Japanese

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: CNS hemangioblastoma, retinal angioma, renal cell carcinoma and pancreatic cyst or tumor (unspecified).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q96_P97delinsH (c.288_290del)

LegacyVariant: c.501_503del

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2573106244, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.288_290del

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion; deletion

CivicName: Q96_P97delinsH (c.288_290del)

MultipleGeneVariants: N/A

A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot analysis of peripheral blood samples. The Q73Rfs*86 (c.217del) germline mutation was found in a VHL type 1 patient with hemangioblastomas of the central nervous system and retinal angiomas (family ID 98). The variant was reported as c.428del and mapped to c.215del which is equivalent to c.217del.

PatientID: 2

KindredID: 1

Case: F, 36Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Patient’s 51Y0M mother also carried the same VHL mutation and had relapsing-remitting multiple sclerosis (MS) in the background of VHL disease. She was diagnosed with hemangioblastomas in the spinal cord and cerebellum, renal cell carcinoma, pancreatic neoplasm and a left ovarian dermoid cyst. She also exhibited vision loss in 1993 and then developed left lower extremity muscle weak in 2007. The limb weakness worsened in 2012 and decreased vision for 2 months, which raised a diagnosis of MS. Since then, treatment with corticosteroids showed partial response of symptoms and Copaxone was then initiated for treating MS. Their family history was significant for multiple cancers in prior generations. Her three sons were also affected by VHL disease, but no mention of genetic testing in these individuals. (see Fig.2 for Pedigree).

CasePresentingHPOs: HP:0006880; HP:0009711; HP:0002666; HP:0030405; HP:0005584; HP:0000572 (Cerebellar Hemangioblastoma; Retinal capilllary Hemangioma; Pheochromocytoma; Pancreatic neuroendocrine tumor; Renal Cell Carcinoma, vision loss)

CaseHPOFreeText: Patient daughter also carried the same VHL mutation and had relapsing-remitting multiple sclerosis (MS) in the background of VHL disease. She had retinal and cerebellar hemangioblastomas, pheochromocytoma, pancreatic neuroendocrine tumor, and recurrent renal cell carcinoma. She exhibited numbness in her limbs and developed vision loss.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID: N/A

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

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R167Q (c.500G>A)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 54

Case: Sex, Age, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: another member of the family (54/1) was detected with an HB and the same mutation

CasePresentingHPOs: HP:0006880 (hemangioblastoma)

CaseHPOFreeText: one RCC tumor was detected in this patient

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R177Dfs*25 (c.528delG)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.176 FS (c.741delG)

ClinVarID: N/A

CAID: CA432423454 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.528delG

gnomAD: N/A

VariantEvidence: LOH detected.

MutationType: minus_1_frameshift_variant

CivicName: R177fs (c.528delG)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 48

Case: Sex, Age, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

CaseHPOFreeText: one RCC tumor was detected in this patient

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F76del (c.227delTCT)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.F76del (c.440delTCT)

ClinVarID: N/A

CAID: CA357012 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.226_228delTTC

gnomAD: N/A

VariantEvidence: LOH detected.

MutationType: deletion

CivicName: F76del (c.227delTCT)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 54

Case: Sex, Age, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: another member (54/2) of the family was detected with an HB and the same mutation

CasePresentingHPOs: HP:0006880 (hemangioblastoma)

CaseHPOFreeText: one RCC tumor was detected in this patient

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R177Dfs*25 (c.528delG)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.176 FS (c.741delG)

ClinVarID: N/A

CAID: CA432423454 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.528delG

gnomAD: N/A

VariantEvidence: LOH detected.

MutationType: minus_1_frameshift_variant

CivicName: R177fs (c.528delG)

MultipleGeneVariants: N/A

PatientID: 6

KindredID: A (III-13)

Case: F, 30Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient's mother (II:7) carried the VHL mutation and presented with hemangioblastoma, renal cell carcinoma, pheochromocytoma, and renal cysts. The patient had two brothers who both carried the mutation, one (III:12) presented with renal cell carcinoma, the other (III:11) with hemangioblastoma, renal cell carcinoma, renal cyst, and retinal capillary hemangioma. The patient also had one asymptomatic sister (III:10) who did not undergo genetic testing. On the mother's side of the family there was extensive history of VHL disease. Refer to Figure 1 for family pedigree and information regarding extended family members.

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

CasePresentingHPOs: HP:0010797, HP:0005584, HP:0009711 (hemangioblastoma, renal cell carcinoma, retinal capillary hemangioma)

CaseHPOFreeText: Diagnosed with hemangioblastoma at age 20. At 24, she was diagnosed with renal cell carcinoma. She underwent nephron-sparing surgery of the left side and one RCC measuring 2 cm in diameter was removed.

CaseNotHPOs: HP:0002666, HP:0000107 (pheochromocytoma, renal cyst)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V170D (c.509T>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 625256 https://www.ncbi.nlm.nih.gov/clinvar/variation/625256/

CAID: N/A

gnomAD: N/A

VariantEvidence:N/A

MutationType: missense_variant;transversion

CivicName: V170D (c.509T>A)

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: 1

KindredID: 1

Case: F, 17Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: N/A - no family history of VHL disease. Authors indicate probably a de novo mutation, however no testing on family members was completed.

CasePresentingHPOs: HP:0006748; HP:0030405; HP:0100615 (pheochromocytoma, pancreatic endocrine tumor, ovarian neoplasm)

CaseHPOFreeText: hospitalized in 2011 (11Y old) due to a hypertensive crisis with end-organ damage (bilateral papilledema and left ventricular hypertrophy). MRI showed 2 heterogenous nodular lesions where the largest was in the right adrenal gland (65x51x39mm) and the other in the left adrenal gland (36x28x25mm). A bilateral adrenalectomy diagnosed both tumors as pheochromocytomas of the adrenal gland. Lymph node metastasis was detected in the adipose tissue surrounding the left adrenal gland. 2 years later (at age 13Y) a PET/CT scan showed a nodular lesion in the tail of the pancreas (11mm) and a nodule in between the inferior vena cava and the portal vein (13mm) and both were later diagnosed as neuroendocrine tumors the former in the pancreas and the latter in the perihaptic ectopic pancreatic tissue. At 14Y, more pancreatic lesions were found. At 16Y, an MRI found a nodule int he right ovary (33mm) which was later diagnosed as a benign ovarian steroid cell tumor

CaseNotHPOs: HP:0010797; HP:0006770 (hemangioblastoma, clear cell renal cell carcinoma)

CaseNotHPOFreeText: Table 1 indicates this was did not have the above manifestations

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R161Q (c.482G>A)

LegacyVariant: p.R161Q (c.695G>A)

CaseProblemVariantFreeText: N/A

ClinVarID: 182983, https://www.ncbi.nlm.nih.gov/clinvar/variation/182983/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R161Q (c.482G>A)

MultipleGeneVariants: N/A