GroupID: 146

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.

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 and/or 8956040. Both these reports include a family presenting with this variant and it is unclear if one or both coincide with the current family.

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: c.564G>T

CaseProblemVariantFreeText: N/A

ClinVarID: 167827, https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

GroupID: 83

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.

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: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: c.564G>T

CaseProblemVariantFreeText: N/A

ClinVarID: 167827, https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

GroupID: V13

DiseaseAssertion: VHL

GroupSize: 4

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: French

GroupAgeRange: N/A

GroupInfo: Patients are grouped by family.

FamilyInfo: 4/8 members of this family that underwent genetic testing had the same mutation.

GroupPresentingHPOs: N/A

GroupHPOFreeText: Diagnosed with VHL Type 1.

GroupNotHPOs: HP:0002666 (Pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 167827, https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: II-1

KindredID: 1

Case: F, Age Unknown (deceased), Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

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

CaseHPOFreeText: Member had clear cell renal carcinomas that were the main cause of mortality, in addition to hemangioblastomas

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: III-9

KindredID: 1

Case: F, Age Unknown, Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

CasePresentingHPOs: HP:0010797; HP:0006770; HP:0009713; HP:0009711; HP:0006880 (hemangioblastoma; clear cell renal cell carcinoma; spinal hemangioblastoma; retinal capillary hemangioma; cerebellar hemangioblastoma)

CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas. She had undergone multiple surgeries because of tumors involving the cerebellum, cervical spine, lumbar spine, multiple abdominal and pelvic organs and the retina. The tumor had been demonstrated on angiography as very extensive and vascular. The patient had had a partial nephrectomy, adrenalectomy, distal pancreatomy for involvement of the tail of the pancreas with a hemangioblastoma and a left salpingoophorectomy.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: III-8

KindredID: 1

Case: F, Age Unknown, Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

CasePresentingHPOs: HP:0010797; HP:0006770; HP:0009725; HP:0030692 (hemangioblastoma; clear cell renal cell carcinoma; bladder tumour; brain tumour)

CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas. She was also the only member of the family to be diagnosed as having a bladder tumor, considered rare in VHL cases, and a brain tumor.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: III-7

KindredID: 1

Case: M, Age Unknown (deceased), Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

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

CaseHPOFreeText: Member had clear cell renal carcinomas that were the main cause of mortality, in addition to hemangioblastomas

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

GroupID/ KindredID: 13F, 564NCI, 1239NCI

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 and the National Cancer Institute database, with an unknown number of members belonging to Family IDs 13F, 564NCI, 1239NCI. 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: 7728151; 9829911

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.W117C (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 4

Case: F, 60Y0M, Ethnicity Unknown

DiseaseAssertion: Clear Cell Renal Cell Carcinoma

FamilyInfo: N/A

CohortInfo: The National Cancer Institute has a frozen tumour bank of ccRCC tumours that have been removed from VHL patients. We selected six patients, three males and three females, with at least five tumours from a single surgery from one kidney.

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

CaseHPOFreeText: The patient presented with ccRCC at age 60.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C(c.351G>X)

LegacyVariant:N/A

CaseProblemVariantFreeText: This protein change corresponds to both c.351G>C or c.351G>T.

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName:W117C(c.351G>X)

MultipleGeneVariants: N/A

GroupID/ KindredID: 15

DiseaseAssertion: assumed VHL

GroupSize: 4

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Chinese

GroupAgeRange: N/A

GroupInfo: With a family history, 4 family members were recorded in this group with the given mutation.

GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0005584; HP:0001732 (hemangioblastoma; retinal capillary hemangioma; renal cell carcinoma; pancreatic lesion)

GroupHPOFreeText: 2 members had CNS hemangioblastomas, 2 had a retinal angiomas, 2 had RCC, 1 had a pancreatic abnormality

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: No family members appeared to have the above manifestation.

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117* (c.351G>A)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.W117* (c.564G>A)

ClinVarID: N/A

CAID: CA351753679 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.351G%3EA

gnomAD: 0.000003976 https://gnomad.broadinstitute.org/variant/3-10188208-G-A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: W117* (c.351G>A)

MultipleGeneVariants: N/A

GroupID: 27

DiseaseAssertion: VHL

GroupSize: 5

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: French

GroupAgeRange: N/A

GroupInfo: 5 patients are listed with this mutation; any relation is unknown.

GroupPresentingHPOs: HP:0009711 (retinal capillary hemangioma)

GroupHPOFreeText: 4 members are said to have retinal HBs. Other manifestations are not clearly stated.

GroupNotHPOs: HP:0009711 (retinal capillary hemangioma)

GroupNotHPOFreeText: the other 1 member is specifically said to not have retinal HBs

GroupPreviousTesting: N/A

PreviouslyPublished: Possibly published in PMID:15300849

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

CaseProblemVariantFreeText: N.A

LegacyVariant: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: W117C (c.351G>T)

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.W117C (c.351G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 83

Case: Sex Unknown, Age Unknown, Japanese

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: Pancreatic cyst or tumor, CNS hemangioblastoma.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: c.564G>T

CaseProblemVariantFreeText: N/A

ClinVarID: 167827, https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 5

Case: M, 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: p.W117C (c.351G>T)

LegacyVariant: c.564G>T (W117C)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827, https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variant is declared as “c.564G>T (W117C)” by the authors, this was treated as a legacy variant and mapped to c.351G>T, W117C. 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: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: III-19

KindredID: 1

Case: F, Age Unknown, Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

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

CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: III-18

KindredID: 1

Case: F, Age Unknown, Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

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

CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: I-1

KindredID: 1

Case: F, Age Unknown (deceased), Persian

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

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

CaseHPOFreeText: Member had clear cell renal carcinomas that were the main cause of mortality, in addition to hemangioblastomas

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 97

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 97

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.W117* (c.351G>A)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.W117* (c.564G>A)

ClinVarID: N/A

CAID: CA351753679 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.351G%3EA

gnomAD: 0.000003976 https://gnomad.broadinstitute.org/variant/3-10188208-G-A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: W117* (c.351G>A)

MultipleGeneVariants: N/A

PatientID: N/A

KindredID: 198

Case: Age unknown, Sex unknown, Ethnicity unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Paper states: Germline, de novo

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes (Specifically Supp. Table S2)

Variant: p.W117Cfs*42 (c.351del)

LegacyVariant: N/A

CaseProblemVariantFreeText: paper states c.350delG which automaps to NM_000551.3:c.351delG

ClinVarID: 223197 https://www.ncbi.nlm.nih.gov/clinvar/variation/223197/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: W117fs (c.351del)

MultipleGeneVariants: N/A

First Witch at 340..351