PatientID: V-PH-05T

KindredID: 3

Case: F, 27Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: No familial cancers/syndromic illnesses

CasePresentingHPOs: HP:0002666; HP:0009711 (pheochromocytoma, retinal capillary hemangioma)

CaseHPOFreeText: diagnosed with recurrent phaeochromocytoma at age 12Y, surgery at 27Y. She also had a personal history of angioma of the right eye, laparotomy & numerous thyrocotomies, and a history of hypertension. Presence of elevated catecholamines, but no further details.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHA, SDHB, SDHC, TMEM127

PreviouslyPublished: 26796762

SupplementalData: Yes (see table S1 and S10)

Variant: p.T157I (c.470C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: Stated as ENSP00000256474.2:p.Thr157Ile

ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: T157I (c.470C>T)

MultipleGeneVariants: Germline, SDHA, c.113A>T (p.Asp38Val)

PatientID: None

KindredID: 11

Case: age, sex, ethnicity unknown

DiseaseAssertion: Unknown

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Described as a positive control but not stated anything further

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: Likely previously published - not clear where the controls came from/ how they were used.

SupplementalData: N/A

Variant: p.T157I (c.470C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: T157I (c.470C>T)

MultipleGeneVariants: N/A

PatientID: 24

KindredID: 24

Case: F, 24Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Negative family history.

CasePresentingHPOs: HP:0002668 (paraganglioma)

CaseHPOFreeText: a carotid body (paraganglioma) was reported with no other details.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T152I (c.455C>T)

CaseProblemVariantFreeText: Variant is written in paper under p.Tyr152Ile. This is incorrect however is paired to a paper where this variant it described (PMID: 18031321) referencing Thr152Ile, so this was deduced.

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA351754382 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.455C%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName:T152I (c.455C>T)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: 11

Case: F, 36Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: There was said to be, at the time, no affected relatives

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

CasePresentingHPOs: HP:0006748; HP:0002668; HP:0006476; HP:0006880; HP:0009711; HP:0000618; HP:0010797 (adrenal pheochorocytoma, paraganglioma, abnormality of the pancreatic islet cells, cerebellar hemangioblastoma, retinal capillary hemangioblastoma, blindness, hemangioblastoma)

CaseHPOFreeText: At 8Y, (in 1978), she was operated for a right pheochromocytoma; at age 13 for a contralateral pheochromocytoma; at age 15, for a 4-cm mass at the neck was diagnosed by selective arteriography as a carotid paraganglioma. The patient was then operated twice for cerebellar hemangioblastoma at age 22, leading to the diagnosis of VHL disease. At age 27, the patient was operated again for a retrocaval pheochromocytoma and for islet cell tumors. The patient was also repeatedly treated for bilateral retinal hemangioblastomas leading to blindness at age 32. At age 36, again a pheochromocytoma was removed

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T157I (c.470C>T)

LegacyVariant: p.T157I

CaseProblemVariantFreeText: The publication only provides the p., the mutation was able to be deduced to p.T157I (c.470C>T)

ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: T157I (c.470C>T)

MultipleGeneVariants: N/A

PatientID: 37

KindredID: 37

Case: F, 26Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: Family positive for VHL. Father presented with CNS hemangioblastoma, pheochromocytoma and further unspecified phenotypes; was diagnosed with VHL Type 2A. Younger sister presented with pheochromocytoma; was diagnosed with VHL Type 2C. Genetic information was not provided for father and sister.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0009711; HP:0002666 (Retinal capillary hemangioma, Pheochromocytoma)

CaseHPOFreeText: Other phenotypes presented but not specified (one or more of: pancreatic cyst or tumor, renal or hepatic cyst). Diagnosed with VHL Type 2A.

CaseNotHPOs: HP:0005584; HP:0010797 (Renal cell carcinoma, Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T157I (c.470C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223223, https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: T157I (c.470C>T)

MultipleGeneVariants: N/A

PatientID: N/A

KindredID: 1

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: paraganglioma

FamilyInfo: N/A

CasePresentingHPOs: HP:0002668 (paraganglioma)

CaseHPOFreeText: Paraganglioma of the head and neck region (HNPGL): Left carotid body; nonsecreting paraganglioma

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: MAX, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T152I (c.455C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351754382 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.455C%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: T152I (c.455C>T)

MultipleGeneVariants: N/A