PatientID: 86

KindredID: 86

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Patient information pulled from Supplemental Table 1b.

Variant: p.L163I (c.487C>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756131

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L163I (c.487C>A)

MultipleGeneVariants: N/A

PatientID: 20

KindredID: 10

Case: M, 42Y0M, Indian

DiseaseAssertion: VHL

FamilyInfo: No relevant family history.

CohortInfo: This retrospective study was conducted at Department of Endocrinology of a tertiary care health centre in Western India. Patients presented to our institute between 2008 and 2016 were included in the study. During the study period a total of 33 patients were suspected to have VHL syndrome based on clinical features among whom 31 patients were found to have mutation in VHL gene. All patients are of Asian Indian descent.

CasePresentingHPOs: HP:0002666; HP:0010797 (Pheochromocytoma, Hemangioblastoma)

CaseHPOFreeText: Unilateral pheochromocytoma.

CaseNotHPOs: HP:0009711; HP:0001737; HP:0005584; HP:0030405; HP:0002668 (Retinal capillary hemangioma, Pancreatic cysts, Renal cell carcinoma, Pancreatic endocrine tumor, Paraganglioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L163F (c.487C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 480772, https://www.ncbi.nlm.nih.gov/clinvar/variation/480772/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L163F (c.487C>T)

MultipleGeneVariants: N/A

PatientID: 60

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.L163H(c.488T>A)

LegacyVariant: c.701T>A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756137

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L163H(c.488T>A)

MultipleGeneVariants: N/A

GroupID/ KindredID: 3682NCI

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 Family ID 3682NCI. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma. Additionally, this family ID is stated again in Table 3 under the mutation c.226T>A. Unclear if this is a typo, or if multiple mutations belong to this one family.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL familywith 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

SupplementalData: N/A

Variant: p.E55Rfs*12 (c.163delG)

LegacyVariant: (c.376delG)

CaseProblemVariantFreeText: N/A

ClinVarID: 428800 https://www.ncbi.nlm.nih.gov/clinvar/variation/428800/

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: minus_1_frameshift_variant

CivicName: E55fs (c.163delG)

MultipleGeneVariants: N/A

CaseExome-2:I-1: Male, Japan, Asian

CaseExome-2:I-1PresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 113 (x (10^9)/l), Platelet Size at 2.7 ± 0.9 (μm), No bleeding tendency

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Father of proband, II-1

CaseSanger-3:I-2: Female, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 132 (x (10^9)/l), Platelet Size at 2.8 ± 0.8 (μm), No bleeding tendency

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Mother of Proband, II-2

CaseExome-2:II-2: Male, Japan, Asian

CaseExome-2:II-2PresentingHPOs: HP:0001873, HP:0040185, HP:0000421 (Thrombocytopenia, Macrothrombocytopenia, Epistaxis)

HPOsFreeText: Platelet Count at 124 (x (10^9)/l), Platelet Size at 2.9 ± 0.9 (μm), No bleeding tendency

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Brother of proband, II-1

CaseSanger-3:II-2: Female, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185, HP:0000421 (Thrombocytopenia, Macrothrombocytopenia, Epistaxis)

HPOsFreeText: Platelet Count at 80 (x (10^9)/l), Platelet Size at 3.0 ± 0.9 (μm), 59% (2.5 μm) aggregation ADP

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Proband of Family Sanger-3

CaseExome-1:II-1: Female, Japan, Asian

CaseExome-1:II-1PresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 91 (x (10^9)/l), Platelet Size at 3.8 ± 1.4 (μm), No bleeding tendency

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CaseExome-2:II-1: Male, Japan, Asian

CaseExome-2:II-1PresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 54 (x (10^9)/l), Platelet Size at 3.1 ± 1.1 (μm), No bleeding tendency, 4.5 min bleeding time, 34% (2 μm) aggregation ADP

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Proband for Family Exome-2

CaseExome-1:I-2: Female, Japan, Asian

CaseExome-1:I-2PresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 80 (x (10^9)/l), Platelet Size at 3.7 ± 1.1 (μm), No bleeding tendency

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Mother of proband, II-1

CaseSanger-1:I-1: Male, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 131 (x (10^9)/l), Platelet Size at 4.2 ± 1.3 (μm), No bleeding tendency, 1 min bleeding time, 49% (2 μm) aggregation ADP

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Father of proband, II-1

CaseSanger-1:II-2: Female, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 97 (x (10^9)/l), Platelet Size at 3.6 ± 1.4 (μm), No bleeding tendency, 74% (2 μm) aggregation ADP

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Sister of Proband, II-1

CaseExome-3:I-2: Female, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 100 (x (10^9)/l), Platelet Size not done, No bleeding tendency

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Mother of proband, II-2

CaseSanger-1:II-1: Female, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 120 (x (10^9)/l), Platelet Size at 3.9 ± 1.6 (μm), No bleeding tendency, 66% (2 μm) aggregation ADP

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Proband for Family Sanger-1

CaseExome-3:II-2: Male, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185, (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 77 (x (10^9)/l), Platelet Size at 2.9 ± 0.6 (μm), No bleeding tendency, 49% (2 μm) aggregation ADP

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Proband for Family Exome-3

CaseSanger-2:III-2: Female, Japan, Asian

CasePresentingHPOs: HP:0001873, HP:0040185 (Thrombocytopenia, Macrothrombocytopenia)

HPOsFreeText: Platelet Count at 77 (x (10^9)/l), Platelet Size at 3.7 ± 1.5 (μm), No bleeding tendency, 2 min bleeding time

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Proband of Family Sanger-2, Had a sister, mother, and grandfather who had the disorder but were not genetically tested to confirm the presence or absence of her variant

CaseF7: Male, Italy

CasePresentingHPOs: HP:0001873 (Thrombocytopenia)

HPOsFreeText: World Health Organization bleeding score is 0 (1 member); Mean platelet count is 110 ×10^9/L; Mean platelet volume is 12.1 fL, Mean platelet diameter is 2.5 μm

CaseAddInfo: N/A

CaseF8P: Italy

CasePresentingHPOs: N/A

CaseAddInfo: Proband for F8

CaseF3:III-2: Female, Italy

CasePresentingHPOs: N/A

CaseAddInfo: Proband for F3

CaseF9: Female, Italy, 48 years diagnosis

CasePresentingHPOs: HP:0001873 (Thrombocytopenia)

HPOsFreeText: World Health Organization bleeding score is 0 (1 members); Mean platelet count is 117 ×10^9/L; Mean platelet volume is 14.4 fL, Mean platelet diameter is 3.3 μm

CaseAddInfo: N/A

CaseF1:III-1: Female, Italy

CasePresentingHPOs: HP:0001634 (Mitral valve prolapse)

CaseAddInfo: Proband for F1

CaseF4:II-1: Male, Italy

CasePresentingHPOs: N/A

CaseAddInfo: Proband for F4

CaseF6:II-1: Male, Italy

CasePresentingHPOs: N/A

CaseAddInfo: Proband for F6

CaseF10:III-1: Italy

CasePresentingHPOs: N/A

CaseAddInfo: Proband for F10

CaseF5:II-2: Male, Italy

CasePresentingHPOs: HP:0001631, HP:0001634 (Atrial septal defect, Mitral valve prolapse)

CaseAddInfo: Proband for F5, 2 other family members share MVP and 5 share ASD

CaseF2:III-1: Female, Italy

CasePresentingHPOs: N/A

CaseAddInfo: Proband for F2

PatientID: 1

KindredID: 1 (A)

Case: M, 15Y0M, Hungarian

DiseaseAssertion: VHL

FamilyInfo: Both parents were healthy with no display of any mutations in the VHL gene, indicating a de novo mutation.

CasePresentingHPOs: HP:0006770; HP:0009711 (clear cell renal cell carcinoma, retinal capillary hemangioma)

CaseHPOFreeText: Patient developed bilateral retinal angioma (retinal capillary hemangioma) and had serious retinal detachment.

CaseNotHPOs: HP:0010797; HP:0002666 (hemangioblastoma, pheochromocytoma)

CaseNotHPOFreeText: MRI of the craniospinal axis could not detect any alterations. No deviation from normal values was observed in the laboratory test.

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E55* (c.163G>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVar: N/A

CAID: CA351748495 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.163G%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: E55* (c.163G>T)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumor)

CaseHPOFreeText: Hereditary PNET with a confirmed germline mutation.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E55Gfs*77 (c.163_164insG)

LegacyVariant: N/A

CaseProblemVariantFreeText: c.163_164insG automapped to NM_000551.3:c.163dupG

ClinVarID: 223159 https://www.ncbi.nlm.nih.gov/clinvar/variation/223159/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant; duplication

CivicName: E55fs (c.163dupG)

MultipleGeneVariants: N/A

PatientID: 12

KindredID: 12

Case: M, 48Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: None

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

CaseHPOFreeText: Bilateral involvements of RCC. 'Other' phenotypes found in patient. These are noted in the paper to include: pancreatic neuroendocrine tumors (PNETs), renal and pancreatic cysts and central nervous system tumors, although it is not clearly stated that patient 1 has all. (See Table 1).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L163P (c.488T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVar: 2231 https://www.ncbi.nlm.nih.gov/clinvar/variation/2231/

CAID: CA020423 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.488T%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: L163P (c.488T>C)

MultipleGeneVariants: N/A