GroupID/ KindredID: 21BMS

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Bristol Myers Squibb database, with an unknown number of members belonging to Family ID 21BMS. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.D121G (c.362A>G)

LegacyVariant: p.D121G (c.575A>G)

CaseProblemVariantFreeText: N/A

ClinVarID: 223200 https://www.ncbi.nlm.nih.gov/clinvar/variation/223200/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: D121G (c.362A>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: 4414NCI, 4577NCI

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the National Cancer Institute database, with an unknown number of members belonging to two family IDs: Family 4414NCI and 4577NCI. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as 2 VHL families with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F119L (c.357C>G)

LegacyVariant: p.F119L (c.570C>G)

CaseProblemVariantFreeText: N/A

ClinVarID: 625240 https://www.ncbi.nlm.nih.gov/clinvar/variation/625240/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: F119L (c.357C>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: 23BMS

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Bristol Myers Squibb database, with an unknown number of members belonging to Family ID 23BMS. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L101R (c.302T>G)

LegacyVariant: p.L101R (c.515T>G)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351751004 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.302T>G

gnomAD: N/A

VariantEvidence: N/A

MutationType: frameshift_variant; transversion

CivicName: L101R (c.302T>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: 137CA

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family ID 137CA. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as a VHL family with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167G (c.499C>G)

LegacyVariant: p.R167G (c.712C>G)

CaseProblemVariantFreeText: N/A

ClinVarID: 2219 https://www.ncbi.nlm.nih.gov/clinvar/variation/2219

CAID: N/A

gnomAD: N/A

VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by location between codons 157 and 189.

MutationType: missense_variant; transversion

CivicName: R167G (c.499C>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: 31CE

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Munich, university of Freiburg and Institute of Pathology database, with an unknown number of members belonging to Family ID 31CE. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: (c.464-2A>G)

LegacyVariant: Splice (c.677-2A>G)

CaseProblemVariantFreeText: N/A

ClinVarID: 223222 https://www.ncbi.nlm.nih.gov/clinvar/variation/223222/

CAID: N/A

gnomAD: N/A

VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by truncating the protein.

MutationType: splice_site_variant

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

MultipleGeneVariants: N/A

GroupID/ KindredID: 4325NCI, 25CA

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the National Cancer Institute databas, and the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family ID 4325NCI and 25CA. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without phechromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL families with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: 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: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: 37CE, 38CE

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Munich, university of Freiburg and Institute of Pathology database, with an unknown number of members belonging to two family IDs: Family 37CE and 38CE. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as multiple VHL families with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L188V (c.562C>G)

LegacyVariant: p.L188V (c.775C>G)

CaseProblemVariantFreeText: N/A

ClinVarID: 2225 https://www.ncbi.nlm.nih.gov/clinvar/variation/2225/

CAID: N/A

gnomAD: 0.00002121 https://gnomad.broadinstitute.org/variant/3-10191569-C-G

VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by location between codons 157 and 189.

MutationType: missense_variant;transversion

CivicName: L188V (c.562C>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: 28BMS

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Bristol Myers Squibb database, with an unknown number of members belonging to family ID: Family 28BMS. Table 5 lists all ID and mutations associated with individuals without detailed clinical information.

GroupPresentingHPOs: N/A

GroupHPOFreeText: Described as multiple VHL families without detailed clinical information. Other phenotypes are possible, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: (c.464-2A>G)

LegacyVariant: Splice (c.677-2A>G)

CaseProblemVariantFreeText: N/A

ClinVarID: 223222 https://www.ncbi.nlm.nih.gov/clinvar/variation/223222/

CAID: N/A

gnomAD: N/A

VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by truncating the protein.

MutationType: splice_site_variant

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

MultipleGeneVariants: N/A

GroupID/ KindredID: 41F

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Neuro Olcologie database in Paris, with an unknown number of members belonging to Family ID 41F. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y156* (c.468T>G)

LegacyVariant: p.Y156* (c.681T>G)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756053 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.468T>G

gnomAD: N/A

VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by truncating the protein.

MutationType: stop_gained

CivicName: Y156* (c.468T>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: 53CE

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Munich, university of Freiburg and Institute of Pathology database, with an unknown number of members belonging to Family ID 53CE. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without phechromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V74G (c.221T>G)

LegacyVariant: p.V74G (c.434T>G)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA70042528 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.221T>G

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: V74G (c.221T>G)

MultipleGeneVariants: N/A

PatientID: 175

KindredID: 69

Case: F, 35Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The male proband, patient 143, was diagnosed with renal cell carcinoma and multiple pancreatic cysts/tumors at age 33. His mother, who was not confirmed with the mutation, had a CNS hemangioblastoma at 30, retinal angioma at 54, and renal cell carcinoma at 50. His sister had a CNS hemangioblastoma at 28, and renal cell carcinoma/ multiple pancreatic cysts/tumors at 35. His niece, who was not confirmed with the mutation, had a CNS hemangioblastoma at age 12. His aunt had a CNS hemangioblastoma at 37, retinal angioma at 45, and renal cell carcinoma at 53. The son of his aunt was asymptomatic at the time of analysis.

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

CaseHPOFreeText: The proband's sister presented with a CNS hemangioblastoma at age 28 and renal cell carcinoma and multiple pancreatic cysts/tumors at age 35.

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.C162W (c.486C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223227; https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: M, 48Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband's son also had this mutation, and presented with a CNS hemangioblastoma at age 22. The proband's mother presented with a CNS hemangioblastoma at age 61, and his brother presented with a CNS hemangioblastoma at age 33. His mother passed away before diagnosis, and there was no DNA sample available for his brother.

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

CaseHPOFreeText: The proband presented with renal cell carcinoma and pancreatic cysts at the age of 48.

CaseNotHPOs: HP:0010797; HP:0009711; HP:0002666 (Hemangioblastoma, Retinal Capillary Hemangioma, Pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

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

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

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID:

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: 6

KindredID: 3

Case: F, 37Y0M, Chinese

DiseaseAssertion: VHL

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

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

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

CaseNotHPOs: HP:0009711; HP:0002666; (Retinal Capillary Hemangioma, Pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

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

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

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID:

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 39

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 39

CasePresentingHPOs: N/A

CaseHPOFreeText: Unknown or unstated.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Unknown evidence for pheochromocytoma (neither yes nor no was stated) in this family

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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: VHL_16 (tumor ID)

KindredID: 16

Case: F, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Adrenal pheochromocytoma

FamilyInfo: N/A

CasePresentingHPOs: HP:0006748 (Adrenal pheochromocytoma)

CaseHPOFreeText: The patient had a benign adrenal pheochromocytoma at an unknown age.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y175C (c.524A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 36905, https://www.ncbi.nlm.nih.gov/clinvar/variation/36905/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: Y175C (c.524A>G)

MultipleGeneVariants: N/A

PatientID: 6

KindredID: 6

Case: 29Y0M, Sex Unknown, Argentinian

DiseaseAssertion: VHL

FamilyInfo: Positive family history

CasePresentingHPOs: HP:0010797; HP:0009711; HP:0001737; HP:0000107 (hemangioblastoma; retinal capillary hemangioma; pancreatic cysts; renal cysts)

CaseHPOFreeText: Aged 22Y at diagnosis (genetic testing); fulfils type 1 VHL clinical diagnosis. CNS and retinal hemangioblastoma was diagnosed at 22, pancreatic cysts and renal cysts were diagnosed at 29Y (See Table 1 & 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: absence of pheochromocytoma/paraganglioma (pheo/pgl) after 14 years of follow-up.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.C162W (c.486C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223227 https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 3618

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: Diagnosed with CNS hemangioblastoma, pheochromocytoma, cysts and VHL Type 2B. Localized pancreatic neuroendocrine tumor is also associated with this family but the number of family members affected is not specified.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 8956040; 7728151

SupplementalData: N/A

Variant: p.C162W (c.486C>G)

LegacyVariant: c.699C>G

CaseProblemVariantFreeText: N/A

ClinVarID: 223227, https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variant reported as 699, C to G (Cys to Trp), assumed to be reported in legacy nomenclature (AF010238.1) and mapped to c.486C>G, p.Cys162Trp (NM_000551.3).

MutationType: missense_variant;transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

PatientID: I (mother)

KindredID: F12

Case: F, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 4 members of this family (I.mother, II.daughter, II.son, III.granddaughter) presented with pheochromocytoma and were found to have the P138= (c.414A>G) germline variant of the VHL gene.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P138= (c.414A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223206, https://www.ncbi.nlm.nih.gov/clinvar/variation/223206/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition; synonymous_variant

CivicName: P138= (c.414A>G)

GroupID: 20B

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: Unknown. Patient was pulled from either the VHL-Registry or NET- Registry and recorded with the given mutation. Symptoms or manifestations are not clear.

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: HP:0030405 (pancreatic endocrine tumor)

CasePreviousTesting: Patient was negatively tested for islet cell tumors (ICTs), or listed as pancreatic endocrine tumor.

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L158V (c.472C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 567944 https://www.ncbi.nlm.nih.gov/clinvar/variation/567944/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: L158V (c.472C>G)

MultipleGeneVariants: N/A

GroupID: 18B

DiseaseAssertion: Unknown. Patients were pulled from either the VHL-Registry or NET-Registry and recorded with the given mutation. Symptoms or manifestations are not clear.

GroupSize: 4

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 4 patients with the given mutation were grouped as group 18(B) in this study. These patients were asymptomatic or unclear of symptoms.

GroupPresentingHPOs: N/A

GroupHPOFreeText: N/A

GroupNotHPOs: HP:0030405 (pancreatic endocrine tumor)

GroupNotHPOFreeText: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.464-2A>G

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223222 https://www.ncbi.nlm.nih.gov/clinvar/variation/223222/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

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

MultipleGeneVariants: N/A

GroupID: 19A

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: None. The patient with the given mutation in this study was a VHL patient with pancreatic ICTs.

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumor)

CaseHPOFreeText: Patient has islet cell tumors (ICTs), or listed as pancreatic endocrine tumor.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y156C (c.467A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43600 https://www.ncbi.nlm.nih.gov/clinvar/variation/43600/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: Y156C (c.467A>G)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

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: p.I151S (c.452T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223215 https://www.ncbi.nlm.nih.gov/clinvar/variation/223215/

CAID: N/A

gnomAD: N/A

VariantEvidence: patient has a germline deletion of VHL gene demonstrated by loss of one open-reading frame signal detected by g7 cDNA probe. Renal cell carcinoma sample from this patient shows a missense somatic mutation I151S(c.452T>G) in the second copy of VHL gene.

MutationType: missense_variant; transversion

CivicName: Deletion AND I151S (c.452T>G)

MultipleGeneVariants: Germline, VHL, deletion

PatientID: 22

KindredID: 22

Case: F, 26Y0M, 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 (Hemangioblastoma)

CaseHPOFreeText: Multiple or bilateral 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:0009711; HP:0005584; HP:0002666 (Retinal capillary hemangioma, Renal cell carcinoma, Pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L101R (c.302T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351751004, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA351751004

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L101R (c.302T>G)

MultipleGeneVariants: N/A

PatientID: 15

KindredID: 15

Case: M, 34Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: None.

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:N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19949673

SupplementalData: N/A

Variant: p.N78S(c.233A>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 93326 https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType:missense_variant;transition

CivicName: N78S(c.233A>G)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: F, 44Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009726; HP:0005562; HP:0009711; HP:0001737; HP:0006770 (Renal neoplasm, Multiple renal cysts, Retinal capillary hemangioma, Pancreatic cysts, Clear cell renal cell carcinoma)

CaseHPOFreeText: Patient 2 was a 44-year-old female with a medical history of asynchronous bilateral solid renal tumors some which were further characterized as clear cell RCC, multiple renal cysts, retinal angioma, pancreatic cysts.

CaseNotHPOs:None

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N78S (c.233A>G)

LegacyVariant: c.446A>G

CaseProblemVariantFreeText: N/A

ClinVar: 93326, https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: CA351749194

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_transition

CivicName: N78S (c.223A>G)

MultipleGeneVariants: N/A

PatientID: 7

KindredID: 7

Case: 55Y0M, Sex unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: Positive -- Their father and brother both had the same germline mutation. Their father was screened after genetic testing and found to have a left RCC with lung metastasis at age 80, and their brother was asymptomatic.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma first presenting at 55Y

CaseNotHPOs: HP:0005584; HP:0002666; HP:0009715 (renal cell carcinoma, pheochromocytoma, Papillary cystadenoma of the epididymis)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

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

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: R107G (c.319C>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 48Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history was unremarkable and proband has no children.

CasePresentingHPOs: HP:0006770; HP:0006880; HP:0001737; HP:0001289; HP:0005584 (Clear cell renal cell carcinoma, Cerebellar hemangioblastoma, Pancreatic cysts, Confusion, Renal cell carcinoma)

CaseHPOFreeText: Presented at age 39 with bilateral renal tumors (2 right side, 3 left side). Pathological evaluation revealed clear cell type renal cell carcinoma (fig. 1, B). After 2 years multiple pancreatic cysts were noted. Two years later 6 bilateral renal cell carcinoma lesions developed. Five years later at age 48 years mental confusion developed and brain MRI showed a cerebellar lesion; histological evaluation revealed cerebellar hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: ex. p.C162W (c.486C>G)

LegacyVariant: c.699C>G

CaseProblemVariantFreeText: N/A

ClinVarID: 223227, https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

GroupID: None

Case: Sex Unknown, 15Y0M, Dutch

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009713 (Spinal hemangioblastoma)

CaseHPOFreeText: Diagnosed with VHL Type 1.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 31087189

SupplementalData: N/A

Variant: p.R120G (c.358A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223199, https://www.ncbi.nlm.nih.gov/clinvar/variation/223199/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R120G (c.358A>G)

MultipleGeneVariants: N/A

GroupID: 66

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 have identical variants. This mutation (c.346C>G) was found in 1 VHL family with 3 patients.

GroupPresentingHPOs: HP:0009711 (retinal capillary hemangioma)

GroupHPOFreeText: 3 patients had retinal capillary hemangioma (RH), with a mean age of diagnosis of 43Y (RH).

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

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.L116V (c.346C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA351753642 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.346C%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L116V (c.346C>G)

MultipleGeneVariants: N/A

GroupID: 85

Case: 27Y0M, 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.538A>G) was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

CaseHPOFreeText: patient had RCCs diagnosed at 27Y

CaseNotHPOs: HP:0009711; HP:0006880; HP:0002666 (retinal capillary hemangioma; cerebellar hemangioblastoma; pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.I180V (c.538A>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 161401 https://www.ncbi.nlm.nih.gov/clinvar/variation/161401/

CAID: N/A

gnomAD: 0.00001061 https://gnomad.broadinstitute.org/variant/3-10191545-A-G

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: I180V (c.538A>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: 25

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 S1 describes 19 patients with missense mutations, including this patient.

Variant: p.V74G(c.221T>G)

LegacyVariant: c.434T>G

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA70042528

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: V74G (c.221T>G)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 3618

Case: Sex, Age, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Familial VHL stated; although only 1 family member recorded.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 8956040

SupplementalData: N/A

Variant: p.C162W (c.486C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.C233W (c.699C>G)

ClinVarID: 223227 https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: C162W (c.486C>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: II-2

GroupID/ KindredID: 6

Case: Age unknown (deceased), M, Chinese

DiseaseAssertion: hemangioblastoma

FamilyInfo: Positive - 22 family members were recorded with the given mutation. 18 had VHL manifestations while 4 were asymptomatic carriers. See pedigree (Fig 3.), or follow GroupID/KindredID: 6

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584; HP:0009711; HP:0001732; HP:0002666 (Renal cell carcinoma, retinal capillary hemangioma, abnormality of the pancreas, pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N78S (c.233A>G)

CaseProblemVariantFreeText: No VHL gene test was conducted but due to substantial family pedigree history, can assumed with confidence this mutation

LegacyVariant: p.N78S (c.446A>G)

ClinVarID: 93326 https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: N78S (c.233A>G)

MultipleGeneVariants: N/A

PatientID: 6

KindredID: 6

Case: F, 34Y0M, Caucasian

DiseaseAssertion: VHL

FamilyInfo: Positive VHL family history.

CasePresentingHPOs: HP:0002011, HP:0001732, HP:0007850, HP:0012210, HP:0030424 (Morphological central nervous system abnormality, abnormality of the pancreas, retinal vascular proliferation, abnormal renal morphology, epididymal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N78D (c.232A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 625226 https://www.ncbi.nlm.nih.gov/clinvar/variation/625226/

CAID: CA351749284 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.232A%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: N78D (c.232A>G)

MultipleGeneVariants: N/A

PatientID: 21 (Aunt)

KindredID: 1

Case: F, 48Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 9 members of this family were found to harbor the c.193T>G germline variant of the VHL gene. ID 35 was asymptomatic. IDs 1 (proband), 28, 2, 6, 17 and 19 all presented with pheochromocytoma. ID 5 presented with CNS hemangioblastoma, retinal angioma and renal cyst OR tumor (not specified).

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

CaseHPOFreeText: The patient presented with a pheochromocytoma at age 39 and retinal angioma at age 41.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

Variant: p.S65A (c.193T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223160, https://www.ncbi.nlm.nih.gov/clinvar/variation/223160/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65A (c.193T>G)

MultipleGeneVariants: N/A

PatientID: 1 (Proband)

KindredID: 7

Case: M, 12Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 6 members of this family were found to harbor the c.319C>G germline variant of the VHL gene. ID 11 presented with renal and pancreatic abnormalities, pheochromocytoma and other undefined phenotypes. ID 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 2 presented with pancreatic abnormalities. ID 10 presented with CNS hemangioblastoma, pancreatic abnormalities and pheochromocytoma. ID 4 presented with pheochromocytoma.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: The patient presented pheochromocytoma (4Y).

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R107G (c.319C>G)

MultipleGeneVariants: N/A

PatientID: 11 (Father)

KindredID: 7

Case: M, 39Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 6 members of this family were found to harbor the c.319C>G germline variant of the VHL gene. ID 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 1 presented with pheochromocytoma. ID 2 presented with pancreatic abnormalities. ID 10 presented with CNS hemangioblastoma, pancreatic abnormalities and pheochromocytoma. ID 4 presented with pheochromocytoma.

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

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

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R107G (c.319C>G)

MultipleGeneVariants: N/A

PatientID: 6 (Sister)

KindredID: 1

Case: F, 24Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 9 members of this family were found to harbor the c.193T>G germline variant of the VHL gene. ID 35 was asymptomatic. IDs 1 (proband), 28, 2, 17 and 19 all presented with pheochromocytoma. ID 5 presented with CNS hemangioblastoma, retinal angioma and renal cyst OR tumor (not specified). ID 21 presented with retinal angioma and pheochromocytoma.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: The patient presented with a Pheochromocytoma at age 9.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

Variant: p.S65A (c.193T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223160, https://www.ncbi.nlm.nih.gov/clinvar/variation/223160/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65A (c.193T>G)

MultipleGeneVariants: N/A

PatientID: 87

KindredID: 87

Case: M, 38Y0M, Chinese (East Asian)

DiseaseAssertion: Pheochromocytoma

FamilyInfo: No family history.

CasePresentingHPOs: Pheochromocytoma (HP:0002666)

CaseHPOFreeText: Pheochromocytoma symptomatic and diagnosed at age 36Y, 2.3cm in size. 2 years later he underwent PPGL genetic testing.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P138P (c.414A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223206 https://www.ncbi.nlm.nih.gov/clinvar/variation/223206/

CAID: N/A

gnomAD: N/A

VariantEvidence: Described as a pathogenic variant, according to the ACMG guidelines at the time of publication.

MutationType: synonymous_variant; missense_variant;transition

CivicName: P138= (c.414A>G)

MultipleGeneVariants: N/A

KindredID: 7

DiseaseAssertion: VHL

GroupSize: Unknown

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This is a family belonging to prefigure No. 7. They are described as ‘VHL-affected’.

GroupPresentingHPOs: HP:0005584 (renal cell carcinoma)

GroupHPOFreeText: RCC-affected; other manifestations are possible but not clear.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L198R (c.593T>G)

LegacyVariant: p.L269R (c.806T>G)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756545 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.593T%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: L198R (c.593T>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: 150

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: VHL family found to have the c.699C>G (C162W) germline variant of the VHL gene. The number of family members included in this study is not specified.

GroupPresentingHPOs: HP:0002666 (Pheochromocytoma)

GroupHPOFreeText: Number of family affected members is not specified.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 7728151

SupplementalData: N/A

Variant: p.C162W (c.486C>G)

LegacyVariant: c.699C>G

CaseProblemVariantFreeText: N/A

ClinVarID: 223227, https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: F26

Case: Sex unknown, 31Y0M, Spanish

DiseaseAssertion: assumed VHL

FamilyInfo: Noted of familial antecedents of phaeochromocytoma and CNS hemangioblastoma.

CasePresentingHPOs: HP:0009711; HP:0000107 (retinal capillary hemangioma, renal cysts)

CaseHPOFreeText: Age of onset is 31Y0M.

CaseNotHPOs: HP:0006770; HP:0002666; HP:0006880; HP:0001737 (clear cell renal cell carcinoma, pheochromocytoma, cerebellar hemangioblastoma, pancreatic cysts, retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.D121G (c.362A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223200 https://www.ncbi.nlm.nih.gov/clinvar/variation/223200/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: D121G (c.362A>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: F41

Case: Sex unknown, 22Y0M, Spanish

DiseaseAssertion: assumed VHL

FamilyInfo: familial antecedents found; unknown of any additional features to index case relatives

CasePresentingHPOs: HP:0009711; HP:0006770; HP:0006880; HP:0000107; HP:0001737 (retinal capillary hemangioma, clear cell renal cell carcinoma, cerebellar hemangioblastoma, renal cysts, pancreatic cysts)

CaseHPOFreeText: Multiple lesions were found with the patient’s cerebellar hemangioma. Unilateral ccRCC. Age of onset is 22Y0M.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L128R (c.383T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753891 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.383T%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: L128R (c.383T>G)

MultipleGeneVariants: N/A

PatientID: II,4

KindredID: 1

Case: M, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient had significant family history. His mother refused genetic testing but presented with bilateral pohechromocytoma. His father was found to have the same VHL mutation. One of his siblings (patient II,3) was unaffected, while another (patient II,2) was found to have the mutation and presented with bilateral pheochromocytoma. His sibling (patient II,1) passed during childbirth with symptoms and signs of a hypertensive crisis with the autopsy showing a left adrenal and extraadrenal pheochromocytoma. However, cause of death was a cerebral hemorrhage. His half sister (patient II,5) also had the same VHL mutation and presented with bilateral pheochromocytoma. Refer to figure 1 for family pedigree.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: bilateral pheochromocytoma

CaseNotHPOs: HP:0006737 (Extraadrenal pheochromocytoma)

CaseNotHPOFreeText: Absence of extraadrenal pheochromocytoma. Absence of thyroid disease at age 24.

CasePreviousTesting: RET

PreviouslyPublished: 7563486, 12414898

SupplementalData: N/A

Variant: p.L188V (c.562C>G)

LegacyVariant: p.L259V (c.775C>G)

CaseProblemVariantFreeText: N/A

ClinVar: 2225 https://www.ncbi.nlm.nih.gov/clinvar/variation/2225/

CAID: N/A

gnomAD: 0.00002121 https://gnomad.broadinstitute.org/variant/3-10191569-C-G

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L188V (c.562C>G)

MultipleGeneVariants: N/A

GroupID/ KindredID: VHL 31

Case: Sex unknown, Age unknown, Italian

DiseaseAssertion: assumed VHL

FamilyInfo: One patient with the given mutation is stated to belong to VHL family 31 - this was said to be not inherited from either parent, indicating a de novo germline mutation.

CasePresentingHPOs: HP:0009711; HP:0010797; HP:0000107; HP:0005584; HP:0001737; HP:0009715 (retinal capillary hemangioma, hemangioblastoma, renal cyst, renal cell carcinoma, pancreatic cysts, papillary cystadenoma of the epididymis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.464-2A>G

CaseProblemVariantFreeText: N/A

LegacyVariant: c.677-2A>G

ClinVarID: 223222 https://www.ncbi.nlm.nih.gov/clinvar/variation/223222/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

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

MultipleGeneVariants: N/A

GroupID/ KindredID: VHL 51

DiseaseAssertion: assumed VHL

GroupSize: 6

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: German

GroupAgeRange: N/A

GroupInfo: 6 patients with the given mutation belonging to VHL family 51

GroupPresentingHPOs: HP:0010797; HP:0009715 (hemangioblastoma, Papillary cystadenoma of the epididymis)

GroupHPOFreeText: CNS hemangioblastomas found in all 6 members of this cohort, and epididimal cystadenomas found in 4 members.

GroupNotHPOs: GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N78S (c.233A>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.N78S (c.446A>G)

ClinVarID: 93326 https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: CA020131 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.233A%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: N78S (c.233A>G)

MultipleGeneVariants: N/A

GroupID: 2

DiseaseAssertion: hemangioblastoma

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 2 out of the 81 patients listed in this hemangioblastoma cohort were found with this c.194C>G mutation. Any relation is unknown.

GroupPresentingHPOs: HP:0010797 (hemangioblastoma)

GroupHPOFreeText: all patients had hemangioblastoma of the CNS; other phenotypes are unknown

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: 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: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: S65W (c.194C>G)

MultipleGeneVariants: N/A

PatientID: III-2

KindredID: 3

Case: F, Age Unknown (deceased), Chinese

DiseaseAssertion: CNS Hemangioblastoma

FamilyInfo: The transition mutation was found and confirmed in 1 patient (II-3) and 2 carriers (III-7, IV-2). 5 members, including III-2, had hemangioblastomas of the CNS, but had all passed away before genetic testing. Could be assumed and deduced the genetics due to pedigree showing future linear relations of this mutation.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L116V (c.346C>G) [assumed]

LegacyVariant: p.L116V (c.559C>G) [assumed]

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753642 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.346C%3EG

gnomAD: N/A

VariantEvidence: No genetic testing was done prior to death, however family history and presentation leads to this deduction

MutationType: missense_variant;transversion

CivicName: L116V (c.346C>G)

MultipleGeneVariants: N/A

PatientID: III-3

KindredID: 3

Case: M, Age Unknown (deceased), Chinese

DiseaseAssertion: CNS Hemangioblastoma

FamilyInfo: The transition mutation was found and confirmed in 1 patient (II-3) and 2 carriers (III-7, IV-2). 5 members, including III-3, had hemangioblastomas of the CNS, but had all passed away before genetic testing. Could be assumed and deduced the genetics due to pedigree showing future linear relations of this mutation.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L116V (c.346C>G) [assumed]

LegacyVariant: p.L116V (c.559C>G) [assumed]

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753642 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.346C%3EG

gnomAD: N/A

VariantEvidence: No genetic testing was done prior to death, however family history and presentation leads to this deduction

MutationType: missense_variant;transversion

CivicName: L116V (c.346C>G)

MultipleGeneVariants: N/A

PatientID: III-1

KindredID: 3

Case: M, Age Unknown (deceased), Chinese

DiseaseAssertion: CNS Hemangioblastoma

FamilyInfo: The transition mutation was found and confirmed in 1 patient (II-3) and 2 carriers (III-7, IV-2). 5 members, including III-1, had hemangioblastomas of the CNS, but had all passed away before genetic testing. Could be assumed and deduced the genetics due to pedigree showing future linear relations of this mutation.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L116V (c.346C>G) [assumed]

LegacyVariant: p.L116V (c.559C>G) [assumed]

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753642 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.346C%3EG

gnomAD: N/A

VariantEvidence: No genetic testing was done prior to death, however family history and presentation leads to this deduction

MutationType: missense_variant;transversion

CivicName: L116V (c.346C>G)

MultipleGeneVariants: N/A

PatientID: III-7

KindredID: 3

Case: F, Age Unknown, Chinese

DiseaseAssertion: asymptomatic

FamilyInfo: The transition mutation was found and confirmed in this patient’s mother (II-3) and 2 carriers, her, and her first-cousin once removed (III-7, IV-2). 5 additional members had hemangioblastomas of the CNS, but had all passed away before genetic testing. Could be assumed and deduced the genetics due to pedigree showing future linear relations of this mutation.

CasePresentingHPOs: N/A

CaseHPOFreeText: Stated as carrier, however she is young (likely before the age of onset)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L116V (c.346C>G)

LegacyVariant: p.L116V (c.559C>G)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753642 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.346C%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L116V (c.346C>G)

MultipleGeneVariants: N/A

GroupID: 87

DiseaseAssertion: VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: French

GroupAgeRange: N/A

GroupInfo: 3 members of this family were found to harbor the c.466T>G germline variant of the VHL gene. Member 4587 presented with severe renal disease (RCC). Members 4588 and 5177 had unknown renal involvement. Families were recruited from the French VHL Registry. Enrolment in the study required identification of the germline VHL mutation (currently 85% of the families included in the French VHL Registry) and available data regarding renal phenotype. A total of 126 families fulfilled these criteria.

GroupPresentingHPOs: HP:0005584 (Renal cell carcinoma)

GroupHPOFreeText: Severe renal disease (any solid lesion before 25 years of age, five or more solid lesions within one or two kidneys, or metastasis of renal cell carcinoma).

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: Paper states that this family is previously reported in PMID 12202531 and/or 9829912, where 1 and 1 individuals respectively with this mutation are reported. It is unclear if one or both of these previously reported groups are the same as the current family.

SupplementalData: Phenotype and genotype information can be found in Supplementary Table S1.

Variant: p.Y156D (c.466T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756043, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.466T%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: Y156D (c.466T>G)

MultipleGeneVariants: N/A

GroupID: 29b

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL CohortInfo: a retrospective cohort study from an eye centre in Germany involved 148 VHL patients and their genetic data involved in retinal capillary hemangiomas.

CasePresentingHPOs: N/A

CaseHPOFreeText: This was 1 of 4 patients discussed with this mutation. The individual did NOT have retinal hemangiomas; Other VHL manifestations were discussed but not per- variant.

CaseNotHPOs: HP:0009711 (retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes - Supplementary Table S1

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: R107G (c.319C>G)

MultipleGeneVariants: N/A

GroupID: 8

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

CohortInfo: a retrospective cohort study from an eye centre in Germany involved 148 VHL patients and their genetic data involved in retinal capillary hemangiomas.

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: This individual patient was the only one discussed with a splice c.464-2A>G mutation. Other VHL manifestations were discussed but not per- variant.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes - Supplementary Table S1

Variant: c.464-2A>G

LegacyVariant: N/A

GroupProblemVariantFreeText: N/A

ClinVarID: 223222 https://www.ncbi.nlm.nih.gov/clinvar/variation/223222/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: spice site (c.464-2A>G)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 5

Case: M, 10Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: (See figure 3E for pedigree). The proband (Patient 5's) mother had left adrenal pheochromocytomas, and his grandmother had bilateral adrenal pheochromocytomas.

CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

CaseHPOFreeText: Proband presented with bilateral adrenal pheochromocytoma

CaseNotHPOs:None

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98C (c.293A>G)

LegacyVariant: N/A

CaseProblemVariant Free Text: N/A

ClinVar: 223176, https://www.ncbi.nlm.nih.gov/clinvar/variation/223176/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_transition

CivicName: Y98C (c.293A>G)

MultipleGeneVariants: N/A

PatientID: 9

KindredID: 8

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: No family information provided.

CasePresentingHPOs: HP:0002666; HP:0002668 (Pheochromocytoma; paraganglioma)

CaseHPOFreeText: Patient had pheochromocytoma and/or paraganglioma (table 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.TF136C (c.407G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant, transversion

CivicName: F136C (c.407T>G)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: No family information provided.

CasePresentingHPOs: HP:0002666; HP:0002668 (Pheochromocytoma; paraganglioma)

CaseHPOFreeText: Patient had pheochromocytoma and/or paraganglioma (table 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R79G (c.235C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 411988, https://www.ncbi.nlm.nih.gov/clinvar/variation/411988/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant, transversion

CivicName: R79G (c.235C>G)

MultipleGeneVariants: N/A

GroupID: None

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales:N/A

GroupNumberFemales:N/A

GroupEthnicity: N/A

GroupAgeRange: ≥12

GroupInfo: The two patients were grouped by mutation.

GroupPresentingHPOs: HP:0001732 (abnormality of the pancreas)

GroupHPOFreeText: N/A

GroupNotHPOs:N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

GroupProblemVariantFreeText: 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: Unknown

KindredID: 4

Case: M, 20Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: This is the proband. 3 members of this family were found to have the mutation and pheochromocytoma. Other declared diseases in this family are: hemangioblastoma, parathyroid nodule, and esophageal carcinoma but the presenting patient is unclear. Relationship between these family members is unclear.

CohortInfo: Patients with the diagnosis of familial or sporadic PHEO and their relatives.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Follow-up 25 years later but it is unclear if this pertained to all affected family members. Pheochromocytoma diagnosed at age 20. VHL type 2C.

CaseNotHPOs: HP:0005584 (Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table 1

Variant: p.P138= (c.414A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223206, https://www.ncbi.nlm.nih.gov/clinvar/variation/223206/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P138= (c.414A>G)

MultipleGeneVariants: N/A

PatientID: Unknown

KindredID: 2

Case: Sex Unknown, 53Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: This is the proband. 5 members of this family were found to have the mutation and pheochromocytoma. Other declared diseases in this family are: paraganglioma, hemangioblastoma, lung metastases and spinal hemangioblastoma but the presenting patient is unclear.Relationship between these family members is unclear.

CohortInfo: Patients with the diagnosis of familial or sporadic PHEO and their relatives.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Follow-up 18 years later but it is unclear if this pertained to all affected family members.

CaseNotHPOs: HP:0005584 (Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table 1

Variant: p.P138= (c.414A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223206, https://www.ncbi.nlm.nih.gov/clinvar/variation/223206/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P138= (c.414A>G)

MultipleGeneVariants: N/A

PatientID: III:2

KindredID: 1

Case: M, 34Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Look to proband (III:3) for extensive family info.

CohortInfo: Patients with the diagnosis of familial or sporadic PHEO and their relatives.

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

CaseHPOFreeText: Unilateral pheochromocytoma diagnosed at age 34.

CaseNotHPOs: HP:0005584 (Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Figure 1

Variant: p.P138= (c.414A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223206, https://www.ncbi.nlm.nih.gov/clinvar/variation/223206/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P138= (c.414A>G)

MultipleGeneVariants: N/A

PatientID: II:5

KindredID: 1

Case: M, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: Look to proband (III:3) for extensive family info.

CohortInfo: Patients with the diagnosis of familial or sporadic PHEO and their relatives.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584 (Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Figure 1

Variant: p.P138= (c.414A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223206, https://www.ncbi.nlm.nih.gov/clinvar/variation/223206/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P138= (c.414A>G)

MultipleGeneVariants: N/A

GroupID: None

KindredID:9

DiseaseAssertion: VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: American Admixed/Latino

GroupAgeRange: N/A

GroupInfo: Three members of a South American family expressed this c.344delA mutation.

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

GroupHPOFreeText: N/A

GroupNotHPOs: HP:0002894, HP:0002666 (neoplasm of the pancreas, pheochromocytoma )

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.H115Pfs*44 (c.344delA)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID:N/A

CAID: CA70049370 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.344delA

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: H115Pfs*44(c.344delA) and P61=(c.183C>G)

MultipleGeneVariants: Germline, VHL,c.c.183C>G (p.Pro61Pro)

GroupID: None

KindredID: 17

DiseaseAssertion: VHL

GroupSize: 10

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: American Admixed /Latino

GroupAgeRange: N/A

GroupInfo: 10 members of a South American family expressed this mutation.

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

GroupHPOFreeText: All 10 family members had a central nervous system hemangioblastoma. One also had a retinal angioma. Five had renal carcinoma. One patient per family with renal tumour <3 cm under follow up detected by imaging.

GroupNotHPOs: HP:0002894, HP:0002666 (neoplasm of the pancreas, pheochromocytoma )

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

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: Partial Deletion and P61=( c.183C>G)

MultipleGeneVariants: Germline, VHL, c.183C>G (Pro61Pro)

GroupID: 5

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Family of 2 VHL Type 1 affected individuals.

GroupPresentingHPOs: HP:0010797 (Hemangioblastoma)

GroupHPOFreeText: CNS hemangioblastoma (2/2 affected members).

GroupNotHPOs: HP:0002894; HP:0009711; HP:0002666; HP:0005584; HP:0009726 (Neoplasm of the pancreas, Retinal capillary hemangioma, Pheochromocytoma, Renal cell carcinoma, Renal neoplasm)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L101R (c.302T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351751004, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.302T%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L101R (c.302T>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: 152

KindredID: 152

Case: Sex Unknown, 24Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None

CasePresentingHPOs: HP:0009711, HP:0001737, HP:0000107 (retinal capillary hemangioma, pancreatic cyst, renal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666, HP:0010797, HP:0006770 (pheochromocytoma, hemangioblastoma, clear cell renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2, S3.

Variant: p.N78S(c.233A>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 93326 https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: CA020131 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.233A%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType:missense_variant;transition

CivicName: N78S(c.233A>G)

MultipleGeneVariants: N/A

PatientID: 55

KindredID: 55

Case: Sex Unknown, 16Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Variant was transmitted from a parent (both parents were analyzed) but it is unclear which parent was positive for the variant.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000107; HP:0006770; HP:0010797; HP:0001732; HP:0009711 (Renal cyst, Clear cell renal cell carcinoma, Hemangioblastoma, Abnormality of the pancreas, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2 and S3

Variant: p.P103A (c.307C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 219823, https://www.ncbi.nlm.nih.gov/clinvar/variation/219823/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: P103A (c.307C>G)

MultipleGeneVariants: N/A

PatientID: 78

KindredID: 78

Case: Sex Unknown, 29Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history noted but details not specified.

CasePresentingHPOs: HP:0001732 (Abnormality of the pancreas)

CaseHPOFreeText: Pancreatic cysts or tumors.

CaseNotHPOs: HP:0006770; HP:0002666; HP:0010797; HP:0009711; HP:0000107 (Clear cell renal cell carcinoma, Pheochromocytoma, Hemangioblastoma, Retinal capillary hemangioma, Renal cyst)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2 and S3

Variant: p.C162W (c.486C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223227, https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

PatientID: 45

KindredID: 45

Case: Sex Unknown, 33Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None

CasePresentingHPOs: HP:0001737, HP:0010797 ( pancreatic cysts, hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666, HP:0006770, HP:0009711, HP:0000107 (pheochromocytoma, clear cell renal cell carcinoma, retinal capillary hemangioma, renal cyst)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2, S3.

Variant: p.N78S(c.233A>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 93326 https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: CA020131 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.233A%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType:missense_variant;transition

CivicName: N78S(c.233A>G)

MultipleGeneVariants: N/A

PatientID: 53

KindredID: 53

Case: Sex Unknown, 37Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history noted but details not specified.

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

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2 and S3

Variant: p.V170G (c.509T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756196, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.509T%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: V170G (c.509T>G)

MultipleGeneVariants: N/A