PatientID: 026

KindredID: 1

Case: F, 25Y0M, Ethnicity Unknown

DiseaseAssertion: pancreatic cancer

FamilyInfo: No family information reported.

CasePresentingHPOs: HP:0002894 (neoplasm of the pancreas)

CaseHPOFreeText: Patient died of pancreatic cancer. No other phenotypic manifestations were detailed (table 1).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E52* (c.154G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182982, https://www.ncbi.nlm.nih.gov/clinvar/variation/182982/

CAID: N/A

gnomAD: 0.00001795, https://gnomad.broadinstitute.org/variant/3-10183685-G-T

VariantEvidence: N/A

MutationType: stop_gained

CivicName: E52* (c.154G>T)

MultipleGeneVariants: N/A

PatientID: 14

KindredID: N/A

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: The authors evaluated 64 VHL patients (32 women and 32 men) with renal involvement of whom 54/64 had undergone renal surgery or a radiofrequency thermal ablation procedure for RCC. In 10/64 VHL patients, at least one or more RCC were diagnosed, however at the time of diagnosis an indication for treatment was not yet present. For all patients several CT/MRI scans existed for retrospective description of tumour growth kinetics.

CasePresentingHPOs: HP:0005584 (Renal cell carcinoma)

CaseHPOFreeText: This is a tumor resolution study (VHL patients were investigated based on the presence of renal tumors.) No other phenotypic information is available.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1 describes 19 patients with missense mutations, including this patient.

Variant: p.P154L (c.461C>T)

LegacyVariant: c.674C>T

CaseProblemVariantFreeText: N/A

ClinVarID: 649525, https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/?new_evidence=true

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

GroupID/ KindredID: 49CA

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family ID 49CA. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as a VHL family with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154L (c.461C>T)

LegacyVariant: p.P154L (c.674C>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 649525 https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

PatientID: II-5

KindredID: B

Case: M, 25Y0M, Ethnicity Unknown

DiseaseAssertion: unknown

FamilyInfo: Two members were confirmed with this germline mutation (II-4 and II-5) c.462A>C and C to T transition at nucleotide 9. Blood from the father (I-1) and one sister (II-2) revealed no mutation. The paper states that the mother (I-2), and two siblings (II-3 and II-6) had died of VHL disease (no further information given though).

CasePresentingHPOs: N/A

CaseHPOFreeText: had clinical VHL manifestations which were not described

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154P (c.462A>C)

LegacyVariant: p.Leu to Leu (c.675A>C)

CaseProblemVariantFreeText: The tumor and blood samples from this patient also showed a C to T transition at nucleotide 9, but this nucleotide change did not alter the amino acid residue encoded and thus appeared to be a polymorphism

ClinVarID: N/A

CAID: CA16621934 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.462A%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: synonymous_variant

CivicName: P154= (c.462A>C)

MultipleGeneVariants: N/A

PatientID: BII:6

KindredID: B

Case: M, 24Y0M (deceased), Chinese

DiseaseAssertion: cerebellar hemangioblastoma

FamilyInfo: A 3-generation family is given with 1 confirmed member tested for VHL (proband: III:5). His mother likely had the mutation as the mother and her brother both had VHL phenotypes at young ages (27Y and 22Y).

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Patient had operation for cerebellar hemangioblastoma at the age of 22 and died of bilateral multiple hemangioblastoma at the age of 24, with no chance of surgical treatment.

CaseNotHPOs: HP:0009711; HP:0002666; HP:0005584; HP:0001737 (retinal capillary hemangioma, pheochromocytoma, renal cell carcinoma, pancreatic cysts)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154L (c.461C>T) [assumed]

LegacyVariant: p.P154L (c.647C>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 649525, https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/

CAID: N/A

gnomAD: N/A

VariantEvidence: No genetic testing was done prior to death, however family history and presentation leads to this assumption

MutationType: missense_variant; transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

PatientID: 49

KindredID: 49

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0100634 (Neuroendocrine neoplasm)

CaseHPOFreeText: Recorded as a pheochromocytoma/paraganglioma

CaseNotHPOs: HP:0010797; HP:0006770; HP:0030405; HP:0009711; HP:0030421 (hemangioblastoma; clear cell renal cell carcinoma; pancreatic neuroendocrine neoplasm, retinal capillary hemangioma, Epididymal neoplasm)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes; see table S1 for VHL subject genetic and manifestation information.

Variant: p.P154L (c.461C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 649525 https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

GroupID: 35

Case: Age unknown, Sex unknown, French

DiseaseAssertion: VHL

FamilyInfo: None - one member documented here

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: other manifestations are not clearly stated.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154P (c.462A>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA16621934 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.462A%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: synonymous_variant

CivicName: P154= (c.462A>C)

MultipleGeneVariants: N/A