17 Matching Annotations
  1. Last 7 days
  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Management of Gene Variants of Unknown Significance: Analysis Method and Risk Assessment of the VHL Mutation p.P81S (c.241C>T)
    3
    1. ClingenBaseline 04 Nov 2026
      his maternal grandmother (71 years)

      PatientID: None

      KindredID: 1

      Case: F, 71Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The patient's father died of acute myeloid leukaemia at age 63. The patient had four children one of whom had the same VHL mutation as her and presented with breast cancer. That child had three sons all of whom carried the VHL mutation. Two of the sons were asymptomatic and one had renal cell carcinoma. The affected son also had a P2P mutation. See Figure 1 for family pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName:P81S (c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline Ethnicity:Danish DiseaseEntity:asymptomatic MutationType:missense_variant;transition CivicName:P81S(c.241C>T) cDNAposition:241 ProteinPosition:81 AminoAcidChange:PROtoSER ClinVarID:2233 ClinVarID:Yes Familial FamilyPedigree AssumedRefSeq:NM_000551.3 ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 02 Nov 2026
      his two brothers (32

      PatientID: None

      KindredID: 1

      Case: M, 32Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The patient's brother carried the mutation and presented with renal cell carcinoma. The patient's paternal uncle died from metastasizing RCC at 46 years of age, and the proband’s father died from urosepsis in relation to bladder cancer in situ at the age of 56. Neither of these men were able to undergo genetic testing. The patient's mother was found to carry the mutation and had breast cancer. The maternal grandmother as well as a half brother were found to harbour the mutation but were asymptomatic. See Figure 1 for family pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName:P81S (c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:asymptomatic Familial FamilyPedigree Ethnicity:Danish ProteinPosition:81 CivicName:P81S(c.241C>T) cDNAposition:241 Mutation:Germline ClinVarID:2233 ClinVarID:Yes MutationType:missense_variant;transition AminoAcidChange:PROtoSER RefSeq:NM_000551.3 ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 02 Nov 2026
      along with a silent mutation p.P2P (c.6C>G) in the VHL gene

      PatientID: None

      KindredID: 1

      Case: M, 31Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: The patient's brother carried the mutation. The proband’s paternal uncle died from metastasizing RCC at 46 years of age, and the proband’s father died from urosepsis in relation to bladder cancer in situ at the age of 56. Neither of these men were able to undergo genetic testing. The patient's mother was found to carry the mutation and had breast cancer. The maternal grandmother as well as a half brother were found to harbour the mutation but were asymptomatic. The proband's child was found to have a different VHL mutation (p.P2P). See Figure 1 for family pedigree.

      CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

      CaseHPOFreeText: The patient presented with renal cell carcinoma at age 29.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P2= (c.6C>G)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 456593 https://www.ncbi.nlm.nih.gov/clinvar/variation/456593/

      CAID: N/A

      gnomAD: 0.000 https://gnomad.broadinstitute.org/variant/3-10183537-C-G

      VariantEvidence: N/A

      MutationType: synonymous_variant

      CivicName: P2=(c.6C>G) and P81S(c.241C>T)

      MultipleGeneVariants: Germline, VHL, c.241C>T (p.Pro81Ser)

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Ethnicity:Danish AssumedRefSeq:NM_000551.3 Familial FamilyPedigree AgeOfPresentation:renalcellcarcinoma:29 DiseaseEntity:renalcellcarcinoma ClinVarID:456593 ClinVarID:Yes MultipleVHLVariants MutationType:synonymous_variant cDNAposition:6 AminoAcidChange:PROtoPRO ProteinPosition:2 CivicName:P2=(c.6C>G)andP81S(c.241C>T) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC5321774/
  3. onlinelibrary-wiley-com.ezproxy.lib.ryerson.ca onlinelibrary-wiley-com.ezproxy.lib.ryerson.ca
    von Hippel-Lindau development in children and adolescents
    5
    1. ClingenBaseline 03 Nov 2026
      19 I 0 5 No manifestations T c.464-?_642 + ?del

      PatientID: I

      KindredID: 19

      Case: Sex Unknown, 5Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: 3 other family members presented with this VHL variant. Patients 19-II and 19-III were asymptomatic. Patient 19-IV presented with 2 retinal hemangioblastomas (10Y and 12Y) and kidney disease (17Y).

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Diagnosed with VHL at age 0Y. Age at the end of study: 5Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: Exon 3 Deletion (c.464-?_642+?del)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: exon_loss_variant

      CivicName: Null (c.464-?_642+?del)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:asymptomatic Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant UnregisteredVariant CivicName:Null(c.464-?_642+?del) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 03 Nov 2026
      II 8 53 2 pheo (8 years) 2 CNS hb (12 + 13 years) 2 retinal hb (8 + 12 years) M c.496G > T (p.Val166Phe)

      PatientID: II

      KindredID: 15

      Case: Sex Unknown, 53Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: 2 other family members presented with the same VHL variant. Patient 15-I was asymptomatic. Patient 15-III presented with 2 pheochromocytoma (15Y).

      CasePresentingHPOs: HP:0002666; HP:0010797; HP:0009711 (Pheochromocytoma, Hemangioblastoma, Retinal capillary hemangioma)

      CaseHPOFreeText: Diagnosed with VHL at age 8Y. Presented with 2 pheochromocytoma (8Y) 2 CNS hb (12Y and 13Y) and 2 retinal hemangioblastomas (8Y, 12Y). Age at the end of study: 53Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pheochromocytoma AgeOfPresentation:hemangioblastoma:12 AgeOfPresentation:hemangioblastoma:13 AgeOfPresentation:retinalcapillaryhemangioma:8 AgeOfPresentation:retinalcapillaryhemangioma:12 AgeOfPresentation:pheochromocytoma:8 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE ClinVarID:2224 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V166F(c.496G>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 02 Nov 2026
      5 I 0 28 1 retinal hb (17 years) T c.433C > T (p.Gln145X)

      PatientID: I

      KindredID: 5

      Case: Sex Unknown, 28Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: 2 family members with the same VHL variant. Patient 5-II presented with 13 CNS hemangioblastomas (11Y, 13Y, 15Y and 17Y), retinal hemangioblastoma (13Y) and 2 pancreatic cysts (16Y). Patient 5-III presented with retinal hemangioblastoma (12Y), pancreatic cysts (12Y), CNS hemangioblastoma (15Y) and kidney disease (12Y).

      CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

      CaseHPOFreeText: Diagnosed with VHL at age 0Y. Presented with retinal hemangioblastoma at 17Y. Age at the end of study: 28Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q145* (c.433C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 625249, https://www.ncbi.nlm.nih.gov/clinvar/variation/625249/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition; stop_gained

      CivicName: Q145* (c.433C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:17 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:433 ProteinPosition:145 AminoAcidChange:GLNtoTER ClinVarID:625249 ClinVarID:Yes MutationType:missense_variant;transition MutationType:stop_gained CivicName:Q145*(c.433C>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    4. ClingenBaseline 02 Nov 2026
      8 I 15 35 6 CNS hb (15 years) 2 retinal hb (15 years) M c.319C > T and c.353 T > C (p.Arg107Cys) and (p.Leu118Pro)

      PatientID: I

      KindredID: 8

      Case: Sex Unknown, 35Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0009711; HP:0010797 (Retinal capillary hemangioma, Hemangioblastoma)

      CaseHPOFreeText: Diagnosed with VHL at age 15Y. Presented with 6 CNS hemangioblastomas (15Y) and 2 retinal hemangioblastomas (15Y). Age at the end of study: 15Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R107C (c.319C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351751195, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.319C%3ET

      gnomAD: 0.000004522, https://gnomad.broadinstitute.org/variant/3-10183850-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R107C (c.319C>T)

      MultipleGeneVariants: Germline, VHL, c.353T>C (p.L118P)

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma AgeOfPresentation:retinalcapillaryhemangioma:15 AgeOfPresentation:hemangioblastoma:15 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:319 ProteinPosition:107 AminoAcidChange:ARGtoCYS ClinVarID:N/A CAID:CA351751195 MutationType:missense_variant;transition CivicName:R107C(c.319C>T) MultipleVHLVariants NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    5. ClingenBaseline 01 Nov 2026
      2 I 0 1 No manifestations M c.388G > A (p.Val130Ile)

      PatientID: I

      KindredID: 2

      Case: Sex Unknown, 1Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: One other family member presented with his VHL mutation and was asymptomatic.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Diagnosed with VHL at age 0Y. Age at the end of study: 1Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V130I (c.388G>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351753916, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.388G%3EA

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: V130I (c.388G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:asymptomatic Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:388 ProteinPosition:130 AminoAcidChange:VALtoILE ClinVarID:N/A CAID:CA351753916 MutationType:missense_variant;transition CivicName:V130I (c.388G>A) Familial inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    URL

    onlinelibrary-wiley-com.ezproxy.lib.ryerson.ca/doi/full/10.1002/ajmg.a.38324
  4. Oct 2026
  5. onlinelibrary-wiley-com.ezproxy.lib.ryerson.ca onlinelibrary-wiley-com.ezproxy.lib.ryerson.ca
    von Hippel-Lindau development in children and adolescents
    7
    1. ClingenBaseline 29 Oct 2026
      18 I 14 48 3 PC (14 years) 1 KD (16 years) T c.606dupA (p.Gln203ThrfsX53)

      PatientID: I

      KindredID: 18

      Case: Sex Unknown, 48Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0001737; HP:0000112 (Pancreatic cysts, Nephropathy)

      CaseHPOFreeText: Diagnosed with VHL at age 14Y. Presented with 3 pancreatic cysts (14Y) and kidney disease (16Y). Age at the end of study: 48Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q203Tfs*53 (c.606dup)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 935385, https://www.ncbi.nlm.nih.gov/clinvar/variation/935385/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: duplication; plus_1_frameshift_variant

      CivicName: Q203TfsX53 (c.606dupA)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:nephropathy DiseaseEntity:pancreaticcysts AgeOfPresentation:nephropathy:16 AgeOfPresentation:pancreaticcysts:14 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:606 ProteinPosition:203 AminoAcidChange:GLNtoTHR ClinVarID:935385 ClinVarID:Yes MutationType:duplication MutationType:plus_1_frameshift_variant CivicName:Q203TfsX53(c.606dupA) NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 24 Oct 2026
      15 I 6 23 No manifestations M c.496G > T (p.Val166Phe)

      PatientID: I

      KindredID: 15

      Case: Sex Unknown, 23Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: 2 other family members presented with the same VHL variant. Patient 15-II presented with 2 pheochromocytoma (8Y) 2 CNS hb (12Y and 13Y) and 2 retinal hemangioblastomas (8Y, 12Y). Patient 15-III presented with 2 pheochromocytoma (15Y).

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Diagnosed with VHL at age 6Y. Age at the end of study: 23Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:asymptomatic Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE ClinVarID:2224 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V166F(c.496G>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    3. ClingenBaseline 23 Oct 2026
      III 10 26 6 PC (15 years) 1 retinal hb (16 years) T c.1-?_340 + ?del

      PatientID: III

      KindredID: 17

      Case: Sex Unknown, 26Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: 2 other family members were found to have this VHL variant. Patient 17-I was asymptomatic. Patient 17-II presented with CNS hemangioblastoma (8Y).

      CasePresentingHPOs: HP:0009711; HP:0001737 (Retinal capillary hemangioma, Pancreatic cysts)

      CaseHPOFreeText: Diagnosed with VHL at age 10Y. Presented with 6 pancreatic cysts (15Y) and retinal hemangioblastoma (16Y). Age at the end of study: 26Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: Exon 1 Deletion (c.1-?_340+?del)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: exon_loss_variant

      CivicName: Exon 1 Deletion

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts AgeOfPresentation:retinalcapillaryhemangioma:16 AgeOfPresentation:pancreaticcysts:15 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant UnregisteredVariant CivicName:Exon1Deletion Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    4. ClingenBaseline 23 Oct 2026
      7 I 4 40 3 retinal hb (8 + 16 years) M c. 499 C > T (p.Arg167Trp)

      PatientID: I

      KindredID: 7

      Case: Sex Unknown, 40Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: One other family member presented with this variant and was asymptomatic.

      CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

      CaseHPOFreeText: Diagnosed with VHL at age 4Y. presented with 3 retinal hemangioblastomas (8Y, 16Y). Age at the end of study: 40Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:8 AgeOfPresentation:retinalcapillaryhemangioma:16 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 MutationType:missense_variant;transition CivicName:R167W (c.499C>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    5. ClingenBaseline 22 Oct 2026
      12 I 5 21 5 retinal hb (5 + 13 + 14 years) 6 CNS hb (15 + 17 years) 3 PC (15 years) T c.l-?_463 + ?del

      PatientID: I

      KindredID: 12

      Case: Sex Unknown, 21Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0009711; HP:0010797; HP:0001737 (Retinal capillary hemangioma, Hemangioblastoma, Pancreatic cysts)

      CaseHPOFreeText: Diagnosed with VHL at age 5Y. Presented with 5 retinal hemangioblastoma (5Y, 13Y, 14Y) 6 CNS hemangioblastoma (15Y, 17Y) 3 pancreatic cysts (15Y). Age at the end of study: 21Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: Exon 1-2 Deletion (c.1-?_463+?del)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: exon_loss_variant

      CivicName: Exon 1-2 Deletion

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:pancreaticcysts AgeOfPresentation:retinalcapillaryhemangioma:5 AgeOfPresentation:retinalcapillaryhemangioma:13 AgeOfPresentation:retinalcapillaryhemangioma:14 AgeOfPresentation:hemangioblastoma:15 AgeOfPresentation:hemangioblastoma:17 AgeOfPresentation:pancreaticcysts:15 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant UnregisteredVariant CivicName:Exon1-2Deletion NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    6. ClingenBaseline 21 Oct 2026
      IV 10 21 2 pheo (12 years) 1 retinal hb (10 years) M c.278G > A (p.Gly93Asp)

      PatientID: IV

      KindredID: 3

      Case: Sex Unknown, 21Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: 3 other family members presented with his VHL mutation. Patient 3-I was asymptomatic. Patients 3-II and 3-III both presented with pheochromocytoma at 15Y.

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

      CaseHPOFreeText: Diagnosed with VHL at age 10Y. Presented with pheochromocytoma at 12Y and retinal hemangioblastoma at 10Y. Age at the end of study: 21Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G93D (c.278G>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 496054, https://www.ncbi.nlm.nih.gov/clinvar/variation/496054/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: G93D (c.278G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:pheochromocytoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:pheochromocytoma:12 AgeOfPresentation:retinalcapillaryhemangioma:10 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:278 ProteinPosition:93 AminoAcidChange:GLYtoASP ClinVarID:496054 ClinVarID:Yes MutationType:missense_variant;transition CivicName:G93D(c.278G>A) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    7. ClingenBaseline 21 Oct 2026
      4 I 7 Dead at age 53 years 2 retinal hb (7 + 14 years) M c.407 T > C (p.Phe136Ser)

      PatientID: I

      KindredID: 4

      Case: Sex Unknown, 53Y0M, Danish

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

      CaseHPOFreeText: Diagnosed with VHL at age 7Y. Presented with retinal hemangioblastoma at 7Y and 14Y. Age of death: 53Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.F136S (c.407T>C)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 496064, https://www.ncbi.nlm.nih.gov/clinvar/variation/496064/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: F136S (c.407T>C)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:7 AgeOfPresentation:retinalcapillaryhemangioma:14 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:407 ProteinPosition:136 AminoAcidChange:PHEtoSER ClinVarID:496064 ClinVarID:Yes MutationType:missense_variant;transition CivicName:F136S(c.407T>C) NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.ezproxy.lib.ryerson.ca/doi/full/10.1002/ajmg.a.38324
  6. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Management of Gene Variants of Unknown Significance: Analysis Method and Risk Assessment of the VHL Mutation p.P81S (c.241C>T)
    2
    1. ClingenBaseline 25 Oct 2026
      his two brothers (32 and 36 years),

      PatientID: None

      KindredID: 1

      Case: M, 36Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The patient's half brothers both carried the mutation, one was asymptomatic and one had renal cell carcinoma. The patient's mother was found to carry the mutation and had breast cancer. The maternal grandmother also harboured the mutation but was asymptomatic. See Figure 1 for family pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName:P81S (c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:asymptomatic Familial FamilyPedigree Ethnicity:Danish ProteinPosition:81 CivicName:P81S(c.241C>T) cDNAposition:241 AminoAcidChange:PROtoSER ClinVarID:2233 ClinVarID:Yes MutationType:missense_variant;transition ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 25 Oct 2026
      proband’s mother (52 years)

      PatientID: None

      KindredID: 1

      Case: F, 52Y0M, Danish

      DiseaseAssertion: Breast carcinoma

      FamilyInfo: The patient had three sons all of whom carried the VHL mutation. Two of the sons were asymptomatic and one had renal cell carcinoma. The affected son also had a P2P mutation and he had a child who was found to have the VHL mutation (P2P). The patient's mother had the mutation but was also asymptomatic. See Figure 1 for family pedigree.

      CasePresentingHPOs: HP:0003002 (Breast carcinoma)

      CaseHPOFreeText: The patient had breast cancer at age 34.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName:P81S (c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:Breastcarcinoma Familial FamilyPedigree Ethnicity:Danish AgeOfPresentation:Breastcarcinoma:34 ProteinPosition:81 CivicName:P81S(c.241C>T) cDNAposition:241 AminoAcidChange:PROtoSER AssumedRefSeq:NM_000551.3 MutationType:missense_variant;transition ClinVarID:2233 ClinVarID:Yes ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5321774/