PatientID: N/A

KindredID: 2

Case: Sex, Age, Ethnicity Unknown

DiseaseAssertion: pheochromocytoma

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: Nonsyndromic pheochromocytoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S68W (c.203C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.S68W (c.416C>G)

ClinVarID: N/A

CAID: CA351748895 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.203C%3EG

gnomAD: N/A

VariantEvidence: PMID: 15611064 shows that S68W nearly completely abolishes the HIF1a hydroxylation dependent binding (Figure 6B) which disrupts HIF-2α degredation in 786-O (renal cell carcinoma) cells (Figure 6 D).

MutationType: missense_variant; transversion

CivicName: S68W (c.203C>G)

MultipleGeneVariants: N/A

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

PatientID: None

KindredID: 3

Case: Unknown, 36Y0M, Chinese

DiseaseAssertion:VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0010797, HP:0005584, HP:0001732 (hemangioblastoma, renal cell carcinoma, abnormality of the pancreas)

CaseHPOFreeText:The patient presented with hemangioblastoma at age 35. One year later he was found to have renal cell carcinoma and pancreatic cysts or tumors.

CaseNotHPOs: HP:0009711, HP:0002666 (retinal capillary hemangioma, pheochromocytoma)

CaseNotHPOFreeText: No epididymal/ovarian cystadenomas.

CasePreviousTesting: N/A

PreviouslyPublished: 29330336

Variant: p.V62Efs*68 (c.185_193delTGCTGCGCTinsAGCA)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID:N/A

CAID: CA2499306941 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499306941

gnomAD:N/A

VariantEvidence: N/A

MutationType: delins

CivicName:V62Efs*68 (c.185_193delTGCTGCGCTinsAGCA)

MultipleGeneVariants: N/A