75 individuals pre-diagnosed with pheochromocytoma and/or paraganglioma were referred for molecular genetic testing. Genomic DNA of each participant was isolated from peripheral blood samples to look for germline mutations in pheochromocytoma and paraganglioma targeted susceptibility genes. 6 targeted genes (IF1B, RET, SDHB, SDHD, TMEM127, and VHL) were sequenced and identified variants were confirmed by sanger sequencing. Sequencing identified a germline S68P(c.202T>C) missense variant in the VHL gene of 3 patients: 4, 5 and 6. Patient 4 (29, M) was pre-diagnosed with pheochromocytoma (bilateral renal and eyes, pancreatic cysts) and had two affected family members, his mother (without any described phenotype or genotype) and his brother (patient 5). Patient 5 (32Y, M) was pre-diagnosed with pheochromocytoma (right kidney-clear cell carcinoma). Lastly, patient 6 was a 33Y male pre-diagnosed with paraganglioma and liver cysts. This patient's cousin was an affected family member described (without genotype or phenotypes details).

PatientID: None

KindredID: 1

Case: M, 29Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: First cousin (male, 33Y) presented with CNS hemangioblastoma, RCC, optic atrophy, vision loss and retinal capillary hemangioblastoma. THis cousin also had the same germline mutation as the proband.

CasePresentingHPOs: HP:0005584; HP:0011531; HP:0009711; HP:0000541 (Renal cell carcinoma, Vitritis, Retinal capillary hemangioma, Retinal detachment)

CaseHPOFreeText: About 1 month previously, percutaneous radiofrequency ablation treatment was performed on the patient due to RCC in his left kidney. Vitritis was detected in the right eye on slit-lamp biomicroscopy. The fundus examination revealed an extensive lipid exudation on the fovea and macula, and a 3-4 optic disc diameter-sized RH at the equator in the right eye; it was normal in the left eye. Optical coherence tomography (OCT) showed that there was a foveal detachment in the right eye.

CaseNotHPOs: HP:0100006 (Neoplasm of the central nervous system)

CaseNotHPOFreeText: Central nervous system involvement was not detected in the patient.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S68P (c.202T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA16621912, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA16621912

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: S68P (c.202T>C)

MultipleGeneVariants: N/A

PatientID: 6

KindredID: 6

Case: M, 39Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: Six unrelated VHL patients with known germline VHL mutations underwent surgery for uni- or bilateral renal lesions.

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

CaseHPOFreeText: The VHL disease affected this patient's CNS, kindey, and eye (not specified). The VHL disease had metastasized. The patient had 1 cyst, 5 solid low-grade passages, 9 solid high-grade passages, and 6 metastatic lymph node passages.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData:N/A

Variant: p.S68P(c.202T>C)

LegacyVariant: p.S68P(c.415T>C)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA16621912 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.202T%3EC

gnomAD: N/A

VariantEvidence: SKY of a high-grade VHL RCC from patient 6, lesion 5, reveals marked aneuploidy and nonreciprocal translocations including der(10)t(9;10), der(19)t(13;19), and der(2)t(2;3) as denoted by arrows.

MutationType: missense_variant;transition

CivicName: S68P (c.202T>C)

MultipleGeneVariants: N/A