GroupID/ KindredID: 110CA

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 110CA. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, ithout phechromocytoma.

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: N/A

SupplementalData: N/A

Variant: p.G57Rfs*75 (c.167_168insA)

LegacyVariant: (c.380insA)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA916084344 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.167_168insA

gnomAD: N/A

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

MutationType: plus_1_frameshift_variant

CivicName: G57fs (c.167_168insA)

MultipleGeneVariants: N/A

PatientID: VHL-6

KindredID: 6

Case: Sex Unknown, Age Unknown, Italian

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

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

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

CaseHPOFreeText: Multiple CNS hemangioblastomas. Clinical classification: A2.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114R (c.340G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

PatientID: None (III)

KindredID: 6

Case: Sex and Ethnicity unknown; Age >18Y0M

DiseaseAssertion: assumed VHL

FamilyInfo: Total of 6 family members belonging to Family 6 (see Table 2; or follow KindredID 6)

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

CaseHPOFreeText: 1 HB, bilateral RA, pancreatic and kidney Cysts during first screening; with the addition of +2 RCC by final status

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 16572651

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: None (VI)

KindredID: 6

Case: Sex and Ethnicity unknown; Age <18Y0M

DiseaseAssertion: Asymptomatic

FamilyInfo: Total of 6 family members belonging to Family 6 (see Table 2; or follow KindredID 6)

CasePresentingHPOs: None

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 16572651

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: None (I)

KindredID: 7

Case: Sex and Ethnicity unknown; Age >18Y0M

DiseaseAssertion: assumed VHL

FamilyInfo: Total of 13 family members belonging to Family 7 (see Table 2; or follow KindredID 7)

CasePresentingHPOs: HP:0030424 (epididymal cyst)

CaseHPOFreeText: Originally thought to be asymptomatic pre-testing; found epididymal cyst at first screening

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: None (V)

KindredID: 6

Case: Sex and Ethnicity unknown; Age <18Y0M

DiseaseAssertion: Asymptomatic

FamilyInfo: Total of 6 family members belonging to Family 6 (see Table 2; or follow KindredID 6)

CasePresentingHPOs: None

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 16572651

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: VHL-16

KindredID: 16

Case: Sex Unknown, Age Unknown, Italian

DiseaseAssertion: VHL

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

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

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

CaseHPOFreeText: Multiple CNS hemangioblastomas. Clinical classification: A1.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114R (c.340G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

GroupID: 23

Case: Age unknown, Sex unknown, French

DiseaseAssertion: VHL

FamilyInfo: None - one member documented here

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: other manifestations are not clearly stated.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: Possibly published in PMID:15300849

SupplementalData: N/A

Variant: p.G114R (c.340G>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 223193 https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

PatientID: None (Child 2)

KindredID: 1

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: Awaiting testing of the proband’s eight siblings to determine whether or not this is a de novo mutation causing VHL disease. Two of three of the proband’s children have inherited the mutation, they have had no disease manifestations.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G144R (c.430G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 576437, https://www.ncbi.nlm.nih.gov/clinvar/variation/576437/

CAID: N/A

gnomAD: 0.000003976, https://gnomad.broadinstitute.org/variant/3-10188287-G-A?dataset=gnomad_r2_1

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: G144R (c.430G>A)

MultipleGeneVariants: N/A

GroupID: 4409

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Each group represents a family.

GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0002666; HP:0005584; HP:0030405 (Retinal capillary hemangioma, Hemangioblastoma, Pheochromocytoma, Renal cell carcinoma, Pancreatic endocrine tumor)

GroupHPOFreeText: 1/2 members with pheochromocytoma, 1/2 members with CNS hemangioblastoma, 2/2 members with retinal angioma, 2/2 members with RCC and 2/2 members with cysts. Diagnosed as a VHL Type 2B family. Metastatic pancreatic neuroendocrine tumor is also associated with this family but the number of family members affected is not specified.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 10458336; 7728151

SupplementalData: N/A

Variant: p.G114R (c.340G>C)

LegacyVariant: c.553G>C

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variant reported as 553, G to C (Gly to Arg), assumed to be reported in legacy nomenclature (AF010238.1) and mapped to c.340G>C, p.Gly114Arg (NM_000551.3).

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

GroupID: 6102

DiseaseAssertion: VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Each group represents a family.

GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0002666; HP:0005584 (Retinal capillary hemangioma, Hemangioblastoma, Pheochromocytoma, Renal cell carcinoma)

GroupHPOFreeText: 1/3 members with pheochromocytoma, 3/3 members with CNS hemangioblastoma, 3/3 members with retinal angioma and 2/3 members with RCC. Diagnosed as a VHL Type 2B family.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114R (c.340G>C)

LegacyVariant: c.553G>C

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variant reported as 553, G to C (Gly to Arg), assumed to be reported in legacy nomenclature (AF010238.1) and mapped to c.340G>C, p.Gly114Arg (NM_000551.3).

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

GroupID: 4409

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

GroupHPOFreeText: all 4 members had retinal angiomas (hemangiomas), 2 had CNS hemangioblastomas, 1 had RCC and 1 had pheochromocytoma

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 10458336

SupplementalData: N/A

Variant: p.G114R (c.340G>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.G185R (c.553G>C)

ClinVarID: 223193 https://www.ncbi.nlm.nih.gov/clinvar/variation/223193

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

PatientID: None (Maternal Grandmother)

KindredID: 1

Case: F, 33Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Look to proband for more information on family history.

CasePresentingHPOs: HP:0006880; HP:0009711 (Cerebellar hemangioblastoma, Retinal capillary hemangioma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 25494863

SupplementalData: Figure 1

Variant: p.G114R (c.340G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD:

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

PatientID: None (Maternal Aunt)

KindredID: 1

Case: F, 30Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Look to proband for more information on family history.

CasePresentingHPOs: HP:0006880; HP:0009711 (Cerebellar hemangioblastoma, Retinal capillary hemangioma)

CaseHPOFreeText: Cerebellar/cerebral trunk hemangioblastoma. Multiple retinal hemangioblastomas.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 25494863

SupplementalData: Figure 1

Variant: p.G114R (c.340G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD:

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

PatientID: None (Proband)

KindredID: 1

Case: M, 18Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The family history revealed VHL in his mother, who died at the age of 40, and in his maternal aunt and grandmother, deceased at 30 and 33 years, respectively. His mother was operated on three times for cerebellar hemangioblastomas, the first at 13 years of age. She had also been treated for bilateral retinal hemangioblastomas since the age of 19. In addition, she had surgery for a renal tumor at the age of 32 and also had pancreatic cysts. She died of the diffuse hemangioblastomas in the posterior fossa. Variant is stated to be previously identified in the family but it is not clear which members have been genetically tested.

CasePresentingHPOs: HP:0006880; HP:0002893; HP:0007663; HP:0001510; HP:0000823; HP:0009711 (Cerebellar hemangioblastoma, Pituitary adenoma, Reduced visual acuity, Growth delay, Delayed puberty, Retinal capillary hemangioma)

CaseHPOFreeText: Referred at the age of 15 for decreased visual acuity of the right eye. Growth failure with short stature for age and lack of pubertal development was noted. This was confirmed by ophthal-mologic examination which also showed bitemporal quadranopsia. Two retinal vascular lesions had already been diagnosed and photocoagulated. Cerebral MRI examination visualized a voluminous pituitary adenoma (confirmed pathologically) with suprasellar extension compressing the optic fibres invading both cavernous sinuses. It also confirmed two small cerebellar hemangioblastomas. On follow-up, MRI showed a persistent pituitary adenoma (confirmed by pathology) with numerous mitoses. A cystic part of the main hemangioblastoma was also noted in the right cerebellum image.

CaseNotHPOs: HP:0005584 (Renal cell carcinoma)

CaseNotHPOFreeText: No renal lesion was found on ultrasound examination. Renal ultrasound examination was persistently normal.

CasePreviousTesting: N/A

PreviouslyPublished: 25494863

SupplementalData: Figure 1

Variant: p.G114R (c.340G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD:

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

PatientID: None (X)

KindredID: 7

Case: Sex and Ethnicity unknown; Age <18Y0M

DiseaseAssertion: Asymptomatic

FamilyInfo: Total of 13 family members belonging to Family 7 (see Table 2; or follow KindredID 7)

CasePresentingHPOs: None

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 16572651

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: None (II)

KindredID: 7

Case: Sex and Ethnicity unknown; Age <18Y0M

DiseaseAssertion: Asymptomatic

FamilyInfo: Total of 13 family members belonging to Family 7 (see Table 2; or follow KindredID 7)

CasePresentingHPOs: None

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 16572651

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: None (XIII)

KindredID: 7

Case: Sex and Ethnicity unknown; Age >18Y0M

DiseaseAssertion: asymptomatic

FamilyInfo: Total of 13 family members belonging to Family 7 (see Table 2; or follow KindredID 7)

CasePresentingHPOs: None

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 16572651

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: 3

KindredID: 5

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Patient’s father is presented with renal cell carcinoma, renal cysts, adrenal pheochromocytoma, spinal hemangioblastoma, pancreatic cysts, endolymphatic sac tumor and salivary gland neoplasm at age 19Y0M. This patient is 1 of 3 carrier children of this mutation, without any further phenotypic information.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93R (c.277G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223174, https://www.ncbi.nlm.nih.gov/clinvar/variation/223174

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant, transversion

CivicName: G93R (c.277G>C)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 5

Case: M, 19Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Patient had 3 carrier children of this mutation, without any further phenotypic information.

CasePresentingHPOs: HP:0005584; HP:0000107; HP:0006748; HP:0009713; HP:0001737; HP:0030939; HP:0100684 (renal cell carcinoma, renal cysts, adrenal pheochromocytoma, spinal hemangioblastoma, pancreatic cysts, endolymphatic sac tumor, salivary gland neoplasm)

CaseHPOFreeText: Patient presented with renal cell carcinoma, renal cysts, adrenal pheochromocytoma, spinal hemangioblastoma, pancreatic cysts, endolymphatic sac tumor and salivary gland neoplasm at age 19Y0M. Patient was diagnosed with VHL type 1 (see table 2).

CaseNotHPOs: HP:0002668; HP:0030405 (paraganglioma; pancreatic endocrine tumor)

CaseNotHPOFreeText: Patient negative for paraganglioma and pancreatic endocrine tumor.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93R (c.277G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223174, https://www.ncbi.nlm.nih.gov/clinvar/variation/223174

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant, transversion

CivicName: G93R (c.277G>C)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 5

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Patient’s father is presented with renal cell carcinoma, renal cysts, adrenal pheochromocytoma, spinal hemangioblastoma, pancreatic cysts, endolymphatic sac tumor and salivary gland neoplasm at age 19Y0M. This patient is 1 of 3 carrier children of this mutation, without any further phenotypic information.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93R (c.277G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223174, https://www.ncbi.nlm.nih.gov/clinvar/variation/223174

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant, transversion

CivicName: G93R (c.277G>C)

MultipleGeneVariants: N/A

PatientID: 22

KindredID: 3816

Case: M, 31Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

CaseHPOFreeText: He presented with one pathologic pancreatic endocrine tumour.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114R (c.340G>C)

LegacyVariant: p.G114R (c.553G>C)

CaseProblemVariantFreeText: N/A

ClinVar: 223193 https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: CA357101 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.340G%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

GroupID: 21

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.340G>C germline variant of the VHL gene. Members 1070 and 744 had unknown renal involvement. Member 742 presented with moderate renal disease (RCC). 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: Moderate renal disease (less than five solid lesions requiring surgical treatment, either unilateral or bilateral).

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: Paper states that this family is previously reported in PMID 12202531, where 2 individuals with this mutation are reported. It is unclear if one or both of these previously reported individuals correspond to members of the current family.

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

Variant: p.G114R (c.340G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD: N/A

VariantEvidence: Authors state that this mutation is predicted to disturb the splicing process.

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A