GroupID: 208

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.T105P (c.313A>C)

LegacyVariant: c.526A>C

CaseProblemVariantFreeText: N/A

ClinVarID: 496055, https://www.ncbi.nlm.nih.gov/clinvar/variation/496055/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: T105P (c.313A>C)

MultipleGeneVariants: N/A

PatientID: N/A

KindredID: 1

Case: F, 42Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Her mother and children have VHL.

CasePresentingHPOs: HP:0009713, HP:0010797, HP:0002666, HP:0030405, HP:0100684 (spinal hemangioblastoma, hemangioblastoma, pheochromocytoma, pancreatic endocrine tumour, salivary gland neoplasm)

CaseHPOFreeText: Patient presented with right sided neck mass that had been causing discomfort for two months. MRI showed a 9-mm rim-enhancing lesion in the right parotid that prompted consideration of malignancy. A parotidectomy revealed a well-demarcated 0.7-cm cyst filled with thick, white to translucent, mucoid material. Histologic examination demonstrated that the cystic tumor with an invasive but well-circumscribed border. The majority of the neoplasm was cystic, and there was no necrosis, appreciable mitotic activity, or cellular pleomorphism or anaplasia, indicative of a low-grade mucoepidermoid carcinoma. She previously had surgical excision of hemangioblastomas of the brain and spinal cord as well as resection of a pheochromocytoma of the left adrenal gland. Additionally, she also had been followed for 2 small pancreatic nodules that were subsequently found to be neuroendocrine tumors. The patient ended up requiring a partial pancreatectomy for a pancreatic neuroendocrine tumour related to her VHL disease.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T105M(c.314C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: Only the protein change was provided in the paper.

ClinVarID: 1057750 https://www.ncbi.nlm.nih.gov/clinvar/variation/1057750/?new_evidence=false

CAID: N/A

gnomAD: 0.000004545 https://gnomad.broadinstitute.org/variant/3-10183845-C-T

VariantEvidence: N/A

MutationType:missense_variant;transition

CivicName:T105M(c.314C>T)

MultipleGeneVariants: Germline, VHL, c.500G>A (p.Arg167Gln)

PatientID: None

KindredID: 5

Case: F, 58Y0M, 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 58.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T105Rfs*54(c.314delC)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432420540 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.314delC

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: T105Rfs*54(c.314delC)

MultipleGeneVariants: N/A

PatientID:6

KindredID: 1

Case: F, 21Y0M, Ethnicity Unknown

DiseaseAssertion: Hemangioblastoma

FamilyInfo: Another member of the patients family (patient 1) had the same VHL gene mutation and presented with hemangioblastoma.

CohortInfo: Thirteen patients with a supratentorial hemangioblastoma.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: The patient presented with splenium of corpus callosum at age 18. The patient was followed up 37 months later.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T105P(c.313A>C)

LegacyVariant:N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 496055 https://www.ncbi.nlm.nih.gov/clinvar/variation/496055/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName:T105P(c.313A>C)

MultipleGeneVariants:N/A

GroupID: V8

DiseaseAssertion: VHL

GroupSize: 14

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: French

GroupAgeRange: N/A

GroupInfo: Patients are grouped by family.

FamilyInfo: 14/27 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.T105P (c.313A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 496055, https://www.ncbi.nlm.nih.gov/clinvar/variation/496055/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: T105P (c.313A>C)

MultipleGeneVariants: N/A

PatientID: 7

KindredID: 7

Case: F, 26Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Positive family history of VHL.

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0000618; HP:0009711; HP:0010797; HP:0002668 (blindness, retinal capillary hemangioma, hemangioblastoma, paraganglioma)

CaseHPOFreeText: At 15Y she presented with loss of visual acuity, leading to the diagnosis of bilateral retinal hemangioblastomas (treated with laser and cryotherapy), with the outcome of unilateral blindness. The patient was then operated 3 times for CNS hemangioblastomas between ages 18 and 24. At age 26, she presented with a palpable lateral neck mass. CT of the head and neck revealed a 3-cm carotid body tumor (paraganglioma).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T105P (c.313A>C)

LegacyVariant: p.T105P

CaseProblemVariantFreeText: As the publication only provides the p., the mutation was deduced to p.T105P (c.313A>C)

ClinVarID: 496055 https://www.ncbi.nlm.nih.gov/clinvar/variation/496055/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: T105P (c.313A>C)

MultipleGeneVariants: N/A