PatientID: 6

KindredID: 6

Case: F, 21Y6M, ethnicity unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: Positive history, with symptomatic father (no mutation known)

CasePresentingHPOs: HP:0006880; HP:0009711; HP:0001737; HP:0000107 (cerebellar hemangioblastoma; retinal capillary hemangioma; pancreatic cysts; renal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.464-1G>T

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 223221 https://www.ncbi.nlm.nih.gov/clinvar/variation/223221/

CAID: N/A

gnomAD: N/A

VariantEvidence: Compound heterozygous: Germline C to G base change at nucleotide 150 of exon 1, and G to T base change at -1 position of splice acceptor sequence for exon 3

MutationType: splice_site_variant

CivicName: [A50= (c.150C>G) and] Splice Site (c.463-1G>T)

MultipleGeneVariants: Germline, VHL, c.150C>G (p.Ala50Ala)

GroupID/ KindredID: VHL 7

DiseaseAssertion: assumed VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Croatian

GroupAgeRange: N/A

GroupInfo: 3 patients with the given mutation belonging to VHL family 7

GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0000107; HP:0001737 (retinal capillary hemangioma, hemangioblastoma, renal cyst, pancreatic cysts)

GroupHPOFreeText: all 3 patients has retinal capillary hemangiomas, but only 1 tally of hemangioblastomas of the central nervous system, renal cysts, and pancreatic cysts were listed.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.463+2T>C

CaseProblemVariantFreeText: The mutation was referred to in the paper as c.676+2C>T - which was corrected to c.676+2T>C with a footnote indicating the correction in relation to Glavac et al Hum Mutat 1996.

LegacyVariant: c.676+2C>T (or correction of c.676+2T>C)

ClinVarID: 569414 https://www.ncbi.nlm.nih.gov/clinvar/variation/569414/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: Splice Site (c.463+2T>C)

MultipleGeneVariants: N/A

PatientID:4

KindredID: 4

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Positive.

CohortInfo:Between September 1994 and December 1997, 16 unrelated individuals were referred to Genetic Services of Western Australia by local clinicians and by similar genetic services in other States, for VHL gene mutation analysis because of clinical manifestations suggestive of the diagnosis.

CasePresentingHPOs: HP:0009711, HP:0010797 (retinal capillary hemangioma, hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666, HP:0005584, HP:0001737 (pheochromocytoma, renal cell carcinoma, pancreatic cysts)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V155M (c.463G>A)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.V155M (c.676G>A)

ClinVarID: 223219 https://www.ncbi.nlm.nih.gov/clinvar/variation/223219/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: V155M (c.463G>A)

MultipleGeneVariants: N/A

PatientID: 242

KindredID: 242

Case: Sex Unknown, 8Y0M, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: Indication of family history.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0009711, HP:0001737, HP:0002666, HP:0006770, HP:0000107, HP:0010797 (retinal capillary hemangioma, pancreatic cyst, pheochromocytoma, clear cell renal cell carcinoma, renal cyst, hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2, S3.

Variant: c.463+1G>A

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 526679 https://www.ncbi.nlm.nih.gov/clinvar/variation/526679/

CAID: N/A

gnomAD: N/A

VariantEvidence: The variant was found to affect the B-domain and disrupt donor splice site intron 2 and lead to abnormal protein folding. The variant was predicted pathogenic.

MutationType: splice_site_variant

CivicName: c.463+1G>A

MultipleGeneVariants: N/A

GroupID: 32

DiseaseAssertion: VHL

GroupSize: 7

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Japanese

GroupAgeRange: N/A

GroupInfo: The seven patients are grouped based on both having the c.463+1G>A mutation. They are unrelated to one another.

GroupPresentingHPOs: HP:0005584, HP:0010797 (renal cell carcinoma, hemangioblastoma)

GroupHPOFreeText: Four of seven members had a hemangioblastoma of the CNS. All seven members had renal cell carcinoma.

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

GroupNotHPOFreeText:N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.463+1G>A

LegacyVariant: c.676G>A

CaseProblemVariantFreeText: N/A

ClinVarID: 526679 https://www.ncbi.nlm.nih.gov/clinvar/variation/526679/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: c.463+1G>A

MultipleGeneVariants: N/A

PatientID: 4

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.V155M(c.463G>A)

LegacyVariant: c.676G>A

CaseProblemVariantFreeText: N/A

ClinVarID: 223219, https://www.ncbi.nlm.nih.gov/clinvar/variation/223219/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: V155M (c.463G>A)

MultipleGeneVariants: N/A

GroupID/ KindredID: 45CE

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 Munich, university of Freiburg and Institute of Pathology database, with an unknown number of members belonging to Family ID 45CE. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: (c.463+1G>C)

LegacyVariant: Splice (c.676+1G>C)

CaseProblemVariantFreeText: N/A

ClinVarID: 223217 https://www.ncbi.nlm.nih.gov/clinvar/variation/223217

CAID: N/A

gnomAD: N/A

VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by truncating the protein.

MutationType: splice_site_variant

CivicName: Splice Site (c.463+1G>C)

MultipleGeneVariants: N/A

PatientID: 13

KindredID: 13

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0006770; HP:0100634; HP:0030405; HP:0009711; HP:0030421 (clear cell renal cell carcinoma; Neuroendocrine neoplasm, 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: c.463+37_463+39del

LegacyVariant: N/A

CaseProblemVariantFreeText: recorded in paper as: Intron 2 +37-39 del TGT. Contacted authors for clarification and confirmation of c.463+37_463+39del

ClinVarID: 223218 https://www.ncbi.nlm.nih.gov/clinvar/variation/223218/

CAID: N/A

gnomAD: 0.0003606 https://gnomad.broadinstitute.org/variant/3-10188351-GGTT-G

VariantEvidence: N/A

MutationType: inframe_insertion


CivicName: c.463+37_463+39del

MultipleGeneVariants: N/A

PatientID: VHL-14

KindredID: 14

Case: Sex Unknown, Age Unknown, Italian

DiseaseAssertion: VHL

FamilyInfo: None.

CohortInfo: Forty-three index cases were referred to the Service of Medical Genetics, Genova, for germline mutation analysis in the VHL gene between 1995 and 2008.

CasePresentingHPOs: HP:0010797, HP:0001737, HP:0009711, HP:0000138 (hemangioblastoma, pancreatic cysts, retinal capillary hemangioma, ovarian cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584, HP:0002666 (Renal cell carcinoma, pheochromocytoma )

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.463+1G>A

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 526679 https://www.ncbi.nlm.nih.gov/clinvar/variation/526679/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: c.463+1G>A

MultipleGeneVariants: N/A

PatientID: VHL 11

KindredID: VHL 11

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: hemangioblastoma

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: Three samples of VHL hemangioblastomas were represented here (.1, .2, .3). They are recorded as both germline and somatic, involving the VHL- and C3ORF10-gene.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A - This sample was likely duplicated in 24132471

SupplementalData: Yes - See Supplementary Table 1

Variant: c.463+3A>C

LegacyVariant: N/A

CaseProblemVariantFreeText: Supplemental data records this as a c.463+3A>C (p.(?)) mutation. The only time the text mentions a splice site mutation however is at: c.463+2T>C p.(?). Will go by supplemental data but be cautious of this discrepancy.

ClinVarID: N/A

CAID: CA645525016 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.463%2B3A%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: Splice Region (c.463+3A>C) 

MultipleGeneVariants: N/A

PatientID: None

KindredID: 6

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: dilatation of the cerebral artery

FamilyInfo: None

CasePresentingHPOs: HP:0004944 (dilatation of the cerebral artery)

CaseHPOFreeText: Patient had an intracranial aneurysm

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.463+8C>T

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 127830 https://www.ncbi.nlm.nih.gov/clinvar/variation/127830/

CAID: N/A

gnomAD: 0.0005055 https://gnomad.broadinstitute.org/variant/3-10188328-C-T

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: Splice Region (c.463+8C>T)

MultipleGeneVariants: N/A

GroupID: 20

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: German

GroupAgeRange: N/A

GroupInfo: 2 registrants from Germany were grouped in this study via the mutation of c.463+2T>C

GroupPresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

GroupHPOFreeText: N/A

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.463+2T>C

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 569414 https://www.ncbi.nlm.nih.gov/clinvar/variation/569414/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: splice_site_variant

CivicName: Splice Site (c.463+2T>C)

MultipleGeneVariants: N/A