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: 194

KindredID: 194

Case: Sex Unknown, 46Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0001732; HP:0002666; HP:0000107 (Hemangioblastoma, Abnormality of the pancreas, Pheochromocytoma, Renal cyst)

CaseHPOFreeText: CNS hemangioblastoma, pancreatic cyst or tumor, pheochromocytoma and renal cystic lesion.

CaseNotHPOs: HP:0009711; HP:0006770 (Retinal capillary hemangioma, Clear cell renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2 and S3

Variant: p.P59Rfs*8 (c.176del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432536374, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.176del

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion; minus_1_frameshift_variant

CivicName: P59fs (c.176delC)

MultipleGeneVariants: N/A