PatientID: 1

KindredID: 1

Case: M, 68Y0M, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0002666; HP:0009711; HP:0000107 (pheochromocytoma, retinal capillary hemangioma, renal cyst)

CaseHPOFreeText: Patient was found observed to have retinal angioma (retinal capillary hemangioma) and a right kidney cortex cyst (30mm). Patient's pheochromocytoma was found incidentally and he remained asymptomatic with steady weight.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHC and SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P25L (c.74C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 93330 https://www.ncbi.nlm.nih.gov/clinvar/variation/93330/

CAID: N/A

gnomAD: 0.002988 https://gnomad.broadinstitute.org/variant/3-10183605-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P25L (c.74C>T)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: M, 68Y0M, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0002666; HP:0009711; HP:0000107 (pheochromocytoma, retinal capillary hemangioma, renal cyst)

CaseHPOFreeText: Patient was found observed to have retinal angioma (retinal capillary hemangioma) and a right kidney cortex cyst (30mm). Patient's pheochromocytoma was found incidentally and he remained asymptomatic with steady weight.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHC and SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P25L (c.74C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 93330 https://www.ncbi.nlm.nih.gov/clinvar/variation/93330/

CAID: N/A

gnomAD: 0.002988 https://gnomad.broadinstitute.org/variant/3-10183605-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P25L (c.74C>T)

MultipleGeneVariants: N/A

PatientID: III:11

KindredID: 1

Case: F, 75, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: The patient's father (II:3) had a brain tumour at age 53 and died at age 78. The patient's paternal aunt (II:1) died of stomach cancer at age 80. The patient's paternal grandfather died at age 50 due to a brain tumour. The patient had seven siblings, five of whom underwent genetic testing. Two were found to carry the mutation but both were asymptomatic (patient III:2 and III:3). The patient's sister (III:2) had three children all of whom carried the P25L mutation and were asymptomatic (IV:4 and IV:6) except patient IV:2 who presented with a retinal hemangioma and renal cyst. Her niece, (IV:2) had three children and one was found to carry the mutation. The patient's brother (III:3) had six children one of whom died due to clear cell renal carcinoma at age 48 but did not carry the P25L mutation (IV:7). The patient had three unaffected children who did not carry the mutation. Of the 13 family members tested, V:2, IV:4, IV:6, III:3, and III:11 were all found to carry the P25L mutation in the VHL gene. Refer to Figure 1 for pedigree.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Ongoing clinical follow up of the individuals with P25L over a period of 5 years has continued to show no evidence of additional clinical involvement of VHL disease.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P25L (c.74C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 93330 https://www.ncbi.nlm.nih.gov/clinvar/variation/93330/

CAID: N/A

gnomAD: 0.002988 https://gnomad.broadinstitute.org/variant/3-10183605-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName:P25L (c.74C>T)

MultipleGeneVariants: N/A

PatientID: III:11

KindredID: 1

Case: F, 75, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: The patient's father (II:3) had a brain tumour at age 53 and died at age 78. The patient's paternal aunt (II:1) died of stomach cancer at age 80. The patient's paternal grandfather died at age 50 due to a brain tumour. The patient had seven siblings, five of whom underwent genetic testing. Two were found to carry the mutation but both were asymptomatic (patient III:2 and III:3). The patient's sister (III:2) had three children all of whom carried the P25L mutation and were asymptomatic (IV:4 and IV:6) except patient IV:2 who presented with a retinal hemangioma and renal cyst. Her niece, (IV:2) had three children and one was found to carry the mutation. The patient's brother (III:3) had six children one of whom died due to clear cell renal carcinoma at age 48 but did not carry the P25L mutation (IV:7). The patient had three unaffected children who did not carry the mutation. Of the 13 family members tested, V:2, IV:4, IV:6, III:3, and III:11 were all found to carry the P25L mutation in the VHL gene. Refer to Figure 1 for pedigree.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Ongoing clinical follow up of the individuals with P25L over a period of 5 years has continued to show no evidence of additional clinical involvement of VHL disease.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P25L (c.74C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 93330 https://www.ncbi.nlm.nih.gov/clinvar/variation/93330/

CAID: N/A

gnomAD: 0.002988 https://gnomad.broadinstitute.org/variant/3-10183605-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName:P25L (c.74C>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 39

Case: Sex Unknown, Age Unknown, Japanese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseHPOFreeText: Retinal angioma.

CaseNotHPOs: HP:0005584; HP:0001732; HP:0010797 (Renal cell carcinoma, Abnormality of the pancreas, Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 8634692

SupplementalData: N/A

Variant: p.P86L (c.257C>T)

LegacyVariant: c.470C>T

CaseProblemVariantFreeText: N/A

ClinVarID: 182977, https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P86L (c.257C>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 39

Case: Sex Unknown, Age Unknown, Japanese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseHPOFreeText: Retinal angioma.

CaseNotHPOs: HP:0005584; HP:0001732; HP:0010797 (Renal cell carcinoma, Abnormality of the pancreas, Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 8634692

SupplementalData: N/A

Variant: p.P86L (c.257C>T)

LegacyVariant: c.470C>T

CaseProblemVariantFreeText: N/A

ClinVarID: 182977, https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P86L (c.257C>T)

MultipleGeneVariants: N/A

PatientID: 249

KindredID: 249

Case: Sex Unknown, 32Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0006770, HP:0000107 (clear cell renal cell carcinoma, renal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0009711,HP:0010797, HP:0001737, HP:0002666 ( retinal capillary hemangioma, hemangioblastoma, pancreatic cyst, pheochromocytoma )

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2, S3.

Variant: p.P86L(c.257C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182977 https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

CAID: CA020186 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.257C%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P86L(c.257C>T)

MultipleGeneVariants: N/A

PatientID: 249

KindredID: 249

Case: Sex Unknown, 32Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0006770, HP:0000107 (clear cell renal cell carcinoma, renal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0009711,HP:0010797, HP:0001737, HP:0002666 ( retinal capillary hemangioma, hemangioblastoma, pancreatic cyst, pheochromocytoma )

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2, S3.

Variant: p.P86L(c.257C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182977 https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

CAID: CA020186 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.257C%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P86L(c.257C>T)

MultipleGeneVariants: N/A

GroupID: 39

Case: Sex Unknown, Age Unknown, Japanese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711(retinal capillary hemangioma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0010797, HP:0002666, HP:0005584 (hemangioblastoma, pheochromocytoma, renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P86L(c.257C>T)

LegacyVariant: p.P157L (c.470C>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 182977 https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P86L(c.257C>T)

MultipleGeneVariants: N/A

GroupID: 39

Case: Sex Unknown, Age Unknown, Japanese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711(retinal capillary hemangioma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0010797, HP:0002666, HP:0005584 (hemangioblastoma, pheochromocytoma, renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P86L(c.257C>T)

LegacyVariant: p.P157L (c.470C>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 182977 https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P86L(c.257C>T)

MultipleGeneVariants: N/A