47 Matching Annotations
  1. Last 7 days
  2. www.liebertpub.com www.liebertpub.com
    VHL Germline Mutations in Argentinian Patients with Clinical Diagnoses or Single Typical Manifestations of Type 1 von Hippel-Lindau Disease
    1
    1. ClingenBaseline 05 Nov 2026
      gross deletions (4/16)

      PatientID: 15

      KindredID: 15

      Case: 34Y0M, Sex Unknown, Argentinian

      DiseaseAssertion: VHL

      FamilyInfo: Positive family history

      CasePresentingHPOs: HP:0006770; HP:0001737; HP:0000107; HP:0030393 (clear cell renal cell carcinoma; pancreatic cysts; renal cyst; endolymphatic sac tumor)

      CaseHPOFreeText: Aged 34Y at diagnosis (genetic testing); fulfils type 1 VHL clinical diagnosis. ccRCC, pancreatic cysts, renal cysts, and endolymphatic sac tumors were all diagnosed at 34Y (See Table 1 & 2).

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: exon 3 deletion

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: exon_loss_variant

      CivicName: Exon 3 Deletion

      MultipleGeneVariants: N/A

      Ethnicity:Argentinian DiseaseEntity:VHL DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst DiseaseEntity:endolymphaticsactumor AgeOfPresentation:clearcellrenalcellcarcinoma:34 AgeOfPresentation:pancreaticcysts:34 AgeOfPresentation:renalcyst:34 AgeOfPresentation:endolymphaticsactumor:34 Mutation:Germline RefSeq:NM_000551.3 CivicName:Exon3Deletion MutationType:exon_loss_variant NonFamilial UnregisteredVariant CAID:N/A ClinVarID:N/A ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    URL

    liebertpub.com/doi/10.1089/gtmb.2016.0204
  3. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Characterization of endolymphatic sac tumors and von Hippel–Lindau disease in the International Endolymphatic Sac Tumor Registry
    11
    1. ClingenBaseline 05 Nov 2026
      1 France delEx2

      GroupID: 37

      Case: Sex unknown, Age unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: Exon 2 deletion

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: exon_loss_variant

      CivicName: Exon 2 Deletion

      MultipleGeneVariants: N/A

      CAID:N/A ClinVarID:N/A UnregisteredVariant CivicName:Exon2deletion MutationType:exon_loss_variant MutationType:deletion DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 Ethnicity:French inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 04 Nov 2026
      1 France c.275A>G p.Asp92Gly

      GroupID: 8

      Case: Sex unknown, Age unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.D92G (c.275A>G)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA351750765 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.275A%3EG

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: D92G (c.275A>G)

      MultipleGeneVariants: N/A

      CAID:CA351750765 ClinVarID:N/A MutationType:missense_variant;transition AminoAcidChange:ASPtoGLY ProteinPosition:92 CivicName:D92G(c.275A>G) cDNAposition:275 DiseaseEntity:endolymphaticsactumor Ethnicity:French DiseaseEntity:VHL Mutation:Germline RefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    3. ClingenBaseline 04 Nov 2026
      2 UK c.332G>A p.Ser111Asn

      GroupID: 11

      DiseaseAssertion: VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: UK (country)

      GroupAgeRange: N/A

      GroupInfo: 2 registrants from the UK were grouped in this study via the mutation of c.332G>A

      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: p.S111N (c.332G>A)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223186 https://www.ncbi.nlm.nih.gov/clinvar/variation/223186/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: S111N (c.332G>A)

      MultipleGeneVariants: N/A

      MutationType:missense_variant;transition cDNAposition:332 ProteinPosition:111 AminoAcidChange:SERtoASN CivicName:S111N(c.332G>A) ClinVarID:223186 ClinVarID:Yes DiseaseEntity:endolymphaticsactumor DiseaseEntity:VHL Mutation:Germline RefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    4. ClingenBaseline 04 Nov 2026
      1 Italy c.470C>T p.Thr157Ile

      GroupID: 22

      Case: Sex unknown, Age unknown, Italian

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      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

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:470 ProteinPosition:157 CivicName:T157I(c.470C>T) AminoAcidChange:THRtoILE MutationType:missense_variant;transition ClinVarID:223223 ClinVarID:Yes Ethnicity:Italian inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    5. ClingenBaseline 03 Nov 2026
      1 Germany c.392A>C p.Asn131Thr

      GroupID: 16

      Case: Sex unknown, Age unknown, German

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N131T (c.392A>C)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA351753944 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.392A%3EC

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: N131T (c.392A>C)

      MultipleGeneVariants: N/A

      CAID:CA351753944 ClinVarID:N/A cDNAposition:392 ProteinPosition:131 AminoAcidChange:ASNtoTHR Ethnicity:German Mutation:Germline RefSeq:NM_000551.3 DiseaseEntity:endolymphaticsactumor DiseaseEntity:VHL MutationType:missense_variant;transversion CivicName:N131T(c.392A>C) inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    6. ClingenBaseline 02 Nov 2026
      3 France c.499C>T p.Arg167Trp UK Germany

      GroupID: 28

      DiseaseAssertion: VHL

      GroupSize: 3

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: French, German, and British

      GroupAgeRange: N/A

      GroupInfo: 3 registrants from were grouped in this study via the mutation of c.499C>T

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

      CaseProblemVariantFreeText: N/A

      LegacyVariant: 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

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      ClinVarID:2218 ClinVarID:Yes CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition Ethnicity:German Ethnicity:French Ethnicity:British DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    7. ClingenBaseline 02 Nov 2026
      1 Spain c.404T>A p.Leu135*

      GroupID: 18

      Case: Sex unknown, Age unknown, Spanish

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.L135* (c.404T>A)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA351754021 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.404T%3EA

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: L135* (c.404T>A)

      MultipleGeneVariants: N/A

      Ethnicity:Spanish DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 ClinVarID:N/A CAID:CA351754021 ProteinPosition:135 cDNAposition:404 MutationType:stop_gained AminoAcidChange:LEUtoTER CivicName:L135*(c.404T>A) inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    8. ClingenBaseline 01 Nov 2026
      1 Italy c.256C>G p.Pro86Ala

      GroupID: 5

      Case: Sex unknown, Age unknown, Italian

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86A (c.256C>G)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 93327 https://www.ncbi.nlm.nih.gov/clinvar/variation/93327/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: P86A (c.256C>G)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:256 ProteinPosition:86 AminoAcidChange:PROtoALA CivicName:P86A(c.256C>G) MutationType:missense_variant;transversion ClinVarID:93327 ClinVarID:Yes Ethnicity:Italian inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    9. ClingenBaseline 01 Nov 2026
      1 Netherlands delEx1

      GroupID: 36

      Case: Sex unknown, Age unknown, Dutch (The Netherlands)

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: Exon 1 deletion

      CaseProblemVariantFreeText: N/A

      LegacyVariant: 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

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 CivicName:Exon1Deletion MutationType:exon_loss_variant MutationType:deletion CAID:N/A ClinVarID:N/A UnregisteredVariant Ethnicity:Dutch inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    10. ClingenBaseline 31 Oct 2026
      1 France c.525C>G p.Tyr175*

      GroupID: 32

      Case: Sex, Age, Ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. One registrant from France has this mutation of c.525C>G

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Y175* (c.525C>G)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 182974 https://www.ncbi.nlm.nih.gov/clinvar/variation/182974/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Y175* (c.525C>G)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline cDNAposition:525 ProteinPosition:175 RefSeq:NM_000551.3 AminoAcidChange:TYRtoTER ClinVarID:182974 CAID:CA020466 MutationType:stop_gained CivicName:Y175*(c.525C>G) ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    11. ClingenBaseline 31 Oct 2026
      1 France c.525C>A p.Tyr175*

      GroupID: 31

      Case: Sex, Age, Ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. One registrant from France has this mutation of c.500C>A

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Y175* (c.525C>A)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA351756231 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.525C%3EA

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Y175* (c.525C>A)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:525 ProteinPosition:175 AminoAcidChange:TYRtoTER CivicName:Y175*(c.525C>A) MutationType:stop_gained CAID:CA351756231 NoFamilyInfo ClinVarID:N/A inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    URL

    onlinelibrary.wiley.com/doi/full/10.1002/hed.24067
  4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Alu-Alu recombination underlies the vast majority of large VHL germline deletions: Molecular characterization and genotype-phenotype correlations in VHL patients
    3
    1. ClingenBaseline 05 Nov 2026
      We identified deletions ranging from 0.5 kb to 250 kb affecting part of or the entire VHL and flanking genes in 54 families.

      GroupID: 45

      DiseaseAssertion: VHL

      GroupSize: N/A GroupNumberMales: N/A GroupNumberFemales: N/A GroupEthnicity: N/A GroupAgeRange: N/A

      GroupInfo: 54 VHL deletion families from the Freiburg registry were selected in order to assist in the correlation of VHL deletions to clinical phenotypes.

      GroupPresentingHPOs: HP:0005584; HP:0000107; HP:0009711; HP:0010797; HP:0009713; HP:0030393; HP:0001737; HP:0030424 (Renal cell carcinoma, Renal cyst, Retinal capillary hemangioma, Hemangioblastoma, Spinal hemangioblastoma, Endolymphatic sac tumor, Pancreatic cysts, Epididymal cyst)

      GroupHPOFreeText: # of affected individuals: Renal cell carcinoma (1), Renal cyst (1), Retinal capillary hemangioma (1), Hemangioblastoma/brain/cerebellum (1), Spinal hemangioblastoma (1), Endolymphatic sac tumor (1), Pancreatic cysts/single cyst (1), Epididymal cyst (1)

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplemental Table 2, Table 1, Table 3

      Variant: Exon 1-3 Deletion (c.1-?_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: Exon 1-3 Deletion

      MultipleGeneVariants: Germline, HSPC300, partial deletion

      MultipleGeneVariants: Germline, ENST197804, deletion

      MultipleGeneVariants: Germline, IRAK2, deletion

      MultipleGeneVariants: Germline, TATDN2, partial deletion

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:renalcyst DiseaseEntity:hemangioblastoma DiseaseEntity:spinalhemangioblastoma DiseaseEntity:pancreaticcysts DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:endolymphaticsactumor DiseaseEntity:epididymalcyst DiseaseEntity:renalcellcarcinoma Mutation:Germline RefSeq:NM_000551.2 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant CivicName:Exon1-3Deletion Familial FamilyCohort MultipleGeneVariants SupplementalData UnregisteredVariant inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 05 Nov 2026
      We identified deletions ranging from 0.5 kb to 250 kb affecting part of or the entire VHL and flanking genes in 54 families.

      GroupID: 26

      DiseaseAssertion: VHL

      GroupSize: N/A GroupNumberMales: N/A GroupNumberFemales: N/A GroupEthnicity: N/A GroupAgeRange: N/A

      GroupInfo: 54 VHL deletion families from the Freiburg registry were selected in order to assist in the correlation of VHL deletions to clinical phenotypes.

      GroupPresentingHPOs: HP:0005584; HP:0000107; HP:0009711; HP:0010797; HP:0009713; HP:0030393; HP:0001737; HP:0030424 (Renal cell carcinoma, Renal cyst, Retinal capillary hemangioma, Hemangioblastoma, Spinal hemangioblastoma, Endolymphatic sac tumor, Pancreatic cysts, Epididymal cyst)

      GroupHPOFreeText: # of affected individuals: Renal cell carcinoma (1), Renal cyst (1), Retinal capillary hemangioma (1), Hemangioblastoma/brain/cerebellum (1), Spinal hemangioblastoma (1), Endolymphatic sac tumor (1), Pancreatic cysts (1), Epididymal cyst (1)

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplemental Table 2, Table 1, Table 3

      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: Exon 3 Deletion

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst DiseaseEntity:spinalhemangioblastoma DiseaseEntity:endolymphaticsactumor DiseaseEntity:epididymalcyst Mutation:Germline RefSeq:NM_000551.2 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant CivicName:Exon3Deletion Familial FamilyCohort SupplementalData UnregisteredVariant inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    3. ClingenBaseline 04 Nov 2026
      We identified deletions ranging from 0.5 kb to 250 kb affecting part of or the entire VHL and flanking genes in 54 families.

      GroupID: 51

      DiseaseAssertion: VHL

      GroupSize: N/A GroupNumberMales: N/A GroupNumberFemales: N/A GroupEthnicity: N/A GroupAgeRange: N/A

      GroupInfo: 54 VHL deletion families from the Freiburg registry were selected in order to assist in the correlation of VHL deletions to clinical phenotypes.

      GroupPresentingHPOs: HP:0005584; HP:0010797; HP:0030393; HP:0030424 (Renal cell carcinoma, Hemangioblastoma, Endolymphatic sac tumor, Epididymal cysts)

      GroupHPOFreeText: # of affected individuals: Renal cell carcinoma (1), Hemangioblastoma/brain/cerebellum (1), Endolymphatic sac tumor (1), Epididymal cysts (1)

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplemental Table 2, Table 1, Table 3

      Variant: Exon 1-3 Deletion (c.1-?_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: Exon 1-3 Deletion

      MultipleGeneVariants: Germline, IRAK2, deletion

      MultipleGeneVariants: Germline, FANCD2, deletion

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:hemangioblastoma DiseaseEntity:endolymphaticsactumor DiseaseEntity:epididymalcyst Mutation:Germline RefSeq:NM_000551.2 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant CivicName:Exon1-3Deletion Familial FamilyCohort MultipleGeneVariants SupplementalData UnregisteredVariant inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/19280651/
  5. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    Frequency of Von Hippel-Lindau germline mutations in classic and non-classic Von Hippel-Lindau disease identified by DNA sequencing, Southern blot analysis and multiplex ligation-dependent probe amplification
    1
    1. ClingenBaseline 04 Nov 2026
      42 c.1-?_642+? Genomic deletion of exons 1 to 3 Familial VHL

      GroupID/ KindredID: 42

      DiseaseAssertion: VHL

      GroupSize: 5

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: 5 registrants belonging to the same family (42) have the germline VHL deletion.

      GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0001737; HP:0000107; HP:0030393 (hemangioblastoma, retinal capillary hemangioma, pancreatic cysts, renal cyst, endolymphatic sac tumor)

      GroupHPOFreeText: 4/5 members had hemangioblastomas, 1 had retinal capillary hemangiomas and renal cysts, 2 had pancreatic cysts, 2 had endolymphatic sac tumors, and 1 had an adnexal papillary tumor of probably mesonephric origin

      GroupNotHPOs: HP:0005584; HP:0002666 (renal cell carcinoma, pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: Exon 1-3 deletion (c.1-?_642+?)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: exon_loss_variant

      CivicName: Exon 1-3 deletion

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.2 CivicName:Exon1-3Deletion MutationType:exon_loss_variant UnregisteredVariant ClinVarID:N/A InheritancePattern:AutosomalDominant Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1111/j.1399-0004.2007.00827.x
  6. journals-scholarsportal-info.myaccess.library.utoronto.ca journals-scholarsportal-info.myaccess.library.utoronto.ca
    Genotype–phenotype analysis of von Hippel–Lindau syndrome in fifteen Indian families
    1
    1. ClingenBaseline 03 Nov 2026
      JK340M?? ??? - ?c.233 A[G

      PatientID: 3

      KindredID: JK

      Case: M, 40Y0M, Indian

      DiseaseAssertion: VHL

      FamilyInfo: One 5 year old female relative (unknown relationship) with the same heterozygous mutation was asymptomatic.

      CasePresentingHPOs: HP:0001737, HP:0010797, HP:0009711, HP:0005584, HP:0030393 (pancreatic cyst, hemangioblastoma, Retinal capillary hemangioma, renal cell carcinoma, endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0002666 (pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N78S (c.233A>G)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 93326 https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_transition

      CivicName: N78S(c.233A>G)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:233 ProteinPosition:78 AminoAcidChange:ASNtoSER ClinVarID:93326 MutationType:missense_variant;transition CivicName:N78S(c.233A>G) Familial Ethnicity:Indian DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:endolymphaticsactumor ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    journals-scholarsportal-info.myaccess.library.utoronto.ca/pdf/13899600/v14i0004/585_gaovhsifif.xml
  7. link.springer.com link.springer.com
    Pheochromocytoma in von hippel-lindau disease: Distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2
    1
    1. ClingenBaseline 03 Nov 2026

      PatientID: 3

      KindredID: 3

      Case: M, 60Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: It is stated that the eight VHL patients were selected from the group of familial VHL patients. Assuming there is family history.

      CohortInfo: Eight patients with VHL disease with pheochromocytoma, eight patients with MEN2 and pheochromocytoma, and 10 sporadic patients.

      CasePresentingHPOs: HP:0006748, HP:0010797, HP:0005584, HP:0030405, HP:0009711, HP:0030393 (adrenal pheochromocytoma, hemangioblastoma, renal cell carcinoma, pancreatic endocrine tumour, retinal capillary hemangioma, endolymphatic sac tumor)

      CaseHPOFreeText: The patient had a right adrenal pheochromocytoma at age 35. The patient had two pheochromocytomas.

      CaseNotHPOs: HP:0008221 (Adrenal hyperplasia)

      CaseNotHPOFreeText: The patient did not have adrenomedullary hyperplasia.

      CasePreviousTesting: N/A

      PreviouslyPublished: Suspected to be, but not mentioned in paper. Paper says, the eight VHL patients were selected from the group of familial VHL patients withknown VHL germline mutations followed on a clinical protocol at the Urologic Oncology Branch, National Cancer Institute, National Institutes of Health (NIH).

      SupplementalData: N/A

      Variant: p.C162W (c.486C>G)

      LegacyVariant: p.C162W (c.699C>G)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223227 https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: C162W (c.486C>G)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:VHL MutationType:missense_variant;transversion AssumedRefSeq:AF010238.1 Familial DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:endolymphaticsactumor AgeOfPresentation:adrenalpheochromocytoma:35 cDNAposition:486 ProteinPosition:162 AminoAcidChange:CYStoTRP ClinVarID:223227 ClinVarID:Yes CivicName:C162W(c.486C>G) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    link.springer.com/article/10.1385/EP:13:1:17
  8. thejns-org.proxy1.lib.uwo.ca thejns-org.proxy1.lib.uwo.ca
    Endolymphatic sac tumors in patients with and without von Hippel—Lindau disease: the role of genetic mutation, von Hippel—Lindau protein, and hypoxia inducible factor-1α expression
    1
    1. ClingenBaseline 01 Nov 2026
      This 32-year-old woman had a family history of VHL disease and her medical history was significant for pancreatic cysts and pheochromocytoma. She experienced headache and dizziness and a temporal bone mass consistent with an ELS tumor was found on brain MR imaging (Fig. 2). A preoperative audiogram showed no hearing function and she underwent a left transcochlear approach and resection of the tumor. The pathological diagnosis was consistent with an ELS tumor. She was later found to have a spinal hemangioblastoma (Fig. 2 right) that was resected and included in this study. Results of genetic testing conducted in the patient and two of her sons were consistent with VHL syndrome and are described later. No evidence of tumor recurrence has been found 2 years after her craniotomy.

      PatientID: 1

      KindredID: 1

      Case: F, 32Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Her two sons and her father had the same VHL mutation.

      CohortInfo:Three patients with endolymphatic sac tumors were studied.

      CasePresentingHPOs: HP:0001737, HP:0002666, HP:0030393, HP:0009713 (pancreatic cysts, pheochromocytoma, endolymphatic sac tumor, spinal hemangioblastoma)

      CaseHPOFreeText: She presented with pancreatic cysts and pheochromocytoma at age 32. She experienced headache and dizziness and a temporal bone mass consistent with an ELS tumor was found on brain MR imaging. A preoperative audiogram showed no hearing function and she underwent a left transcochlear approach and resection of the tumor. The pathological diagnosis was consistent with an ELS tumor. She was later found to have a spinal hemangioblastoma that was resected and included in this study.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: c.464-1G>A

      LegacyVariant: N/A

      CaseProblemVariantFreeText: The paper describes the mutation as "C-to-A transversion at position −1 on the exon 3 splice acceptor sequence in the VHL gene"

      ClinVar: 43603 https://www.ncbi.nlm.nih.gov/clinvar/variation/43603/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: splice_site_variant

      CivicName: Splice Site (c.464-1G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline Familial DiseaseEntity:VHL DiseaseEntity:pancreaticcysts DiseaseEntity:pheochromocytoma DiseaseEntity:endolymphaticsactumor DiseaseEntity:spinalhemangioblastoma AgeofPresentation:pancreaticcysts:32 AgeOfPresentation:pheochromocytoma:32 AgeOfPresentation:endolymphaticsactumor:32 cDNAposition:464 MutationType:splice_site_variant ClinVarID:43603 ClinVarID:Yes AssumedRefSeq:NM_000551.3 ProteinPosition:N/A AminoAcidChange:N/A CivicName:SpliceSite(c.464-1G>A) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    thejns-org.proxy1.lib.uwo.ca/view/journals/j-neurosurg/100/3/article-p488.xml
  9. journals-lww-com.uhn.idm.oclc.org journals-lww-com.uhn.idm.oclc.org
    Endolymphatic Sac Tumor in von Hippel-Lindau Disease : Otology & Neurotology
    1
    1. ClingenBaseline 01 Nov 2026
      The ELST shown in Figure 1 occurred in the left temporal bone of an 8-year-old boy who presented with profound sensorineural hearing loss, intermittent vertigo, and vHL based on mutation analysis that showed a G-to-C nucleotide 601 mutation in the vHL gene on chromosome 3. High-resolution computed tomographic imaging using a bone-window protocol demonstrates a destructive mass involving the posterior aspect of the left petrous temporal bone centered midway between the internal auditory canal and the sigmoid sinus. Bony erosion extends into the posterior semicircular canal, and there are areas of stippling and central calcification within the mass suggestive of an aggressive, erosive process. Magnetic resonance images of ELSTs may demonstrate enhancement on precontrast T1-weighted images and heterogeneous enhancement on T2-weighted images. Larger lesions may show flow voids. Although the diagnosis in this case was relatively straightforward on the basis of the combination of genetic screening studies and characteristic imaging features on computed tomographic scanning, a differential diagnosis of similar lesions should include meningioma, choroid plexus papilloma, paraganglioma, chondrosarcoma, and metastasis.

      PatientID: 1

      KindredID: 1

      Case: M, 8Y0M, Ethnicity Unknown

      DiseaseAssertion: endolymphatic sac tumor (ELST)

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0030393 (endolymphatic sac tumor)

      CaseHPOFreeText: ELST that occurred in the left temporal bone who presented with profound sensorineural hearing loss, intermittent vertigo. A CT demonstrated a destructive mass involving the posterior aspect of the left petrous temporal bone centered midway between the internal auditory canal and the sigmoid sinus. Bony erosion extends into the posterior semicircular canal, and there are areas of stippling and central calcification within the mass suggestive of an aggressive, erosive process

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V130L (c.388G>C)

      LegacyVariant: c.601G>C mutation in the vHL gene on chromosome 3

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2229 https://www.ncbi.nlm.nih.gov/clinvar/variation/2229/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: N/A

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:endolymphaticsactumor AgeOfPresentation:endolymphaticsactumor:8 Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:388 AminoAcidChange:VALtoLEU ProteinPosition:130 MutationType:missense_variant;transversion ClinVarID:2229 ClinVarID:Yes CivicName:N/A NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    journals-lww-com.uhn.idm.oclc.org/otology-neurotology/fulltext/2003/09000/endolymphatic_sac_tumor_in_von_hippel_lindau.24.aspx
  10. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Endolymphatic sac tumor with von Hippel-Lindau disease: report of a case with atypical pathology of endolymphatic sac tumor
    1
    1. ClingenBaseline 30 Oct 2026
      A 42-year-old female was admitted with complaints of a 15-day history of intermittent headaches and dizziness, without nausea and vomiting. Computed tomography (CT) revealed a giant mass lesion with mixed density in the right CPA region along with the destroyed petrous bone (Figure 1A), and a low density space-occupying lesion in the left cerebellar hemisphere. No abnormal physical and laboratory examination including abdominal CT, were found except for a past history of appendicitis excision and cesarean section and the impairment of right hearing resulting from otitis media in childhood. Cranial magnetic resonance imaging (MRI) described two tumors that were 4 × 3 × 3 cm in size in the right CPA region with mixed-signal intensity on T1, T2-weighted images and heterogeneous contrast enhancement; and 4.1 × 2.5 × 3.0 cm in size in the left cerebellar hemisphere with being obviously cystic change (Figure 1B-E). The boundary of two lesions were relatively clear from surrounding parenchyma.Open in a separate windowFigure 1Radiologic characterization of endolymphatic sac tumor and hemangioblastoma. A: CT imaging demonstrated a destroyed petrous bone involving the right mastoid and the middle ear. B-E: MR scan showed two giant masses co-existing in the posterior cranial fossa. The right one in the CPA was irregular, heterogeneous on T1/T2-weighted images as well as heterogeneous contrast enhancement, the left lesion was shown with solid and cyst change in cerebellar hemisphere. F: MRI scan after the second operation showed totally resection of both lesions.Operation and pathological findingsBoth tumors were completely removed via right and left retrosigmoid sinus craniotomy respectively within 25 days. During the first operation, lesion with demarcating from normal cerebellar tissue and invading part of petrous bone were found. The origin of the tumor from petrous bone could be apparently observed. In the second operation, the brown cyst fluid associated with old hemorrhage and soft solid nodule were seen. Under a microscope observation after the first surgery, intense vascularization of the tumor and the obviously primarily cystic architecture were observed. The cystic architecture filled with colloid-like material. Most of them were lined by a single layer of flattened epithelial cells, few covered by a single layer of cuboidal to columnar cells (Figure 2A-D). Immunohistochemical staining demonstrated vascular cells positive reactivity for CD31 (Figure 3A) and CD34 (Figure 3C), which were mistaken for the tumor cells at the initial diagnosis. Subsequently, further immunohistochemical staining showed positive reactivity for PAS (Figure 3B), epithelial membrane antigen (EMA) (Figure 3D), NSE and cytokeratin (CK) but negative for D2-40 and S-100. As to another specimen, histological examination shown round-to-oval nuclei and abundant clear cytoplasms in most of cells (Figure 4). Immunohistochemical staining confirmed hemangioblastoma.

      PatientID: 1

      KindredID: 1

      Case: F, 42Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797; HP:0030393; HP:0002315; HP:0002321 (Hemangioblastoma, Endolymphatic sac tumor, Headache, Vertigo)

      CaseHPOFreeText: Admitted with complaints of a 15-day history of intermittent headaches and dizziness, without nausea and vomiting. Computed tomography (CT) revealed a giant mass lesion with mixed density in the right CPA region along with the destroyed petrous bone, and a low density space-occupying lesion in the left cerebellar hemisphere. Cranial MRI described two tumors in the right CPA region and in the left cerebellar hemisphere. A classic radiological feature of hemangioblastoma was observed in the left cerebellar hemisphere which was supported by post-operative biopsy.

      CaseNotHPOs: HP:0002012 (Abnormality of the abdominal organs)

      CaseNotHPOFreeText: No abnormal physical and laboratory examination, including abdominal CT, were found.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Y98Afs*37 (c.282_291dup)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA2573050500, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA2573050500

      gnomAD: N/A

      VariantEvidence: 291st site of Exon 1 was insertion of 10 nucleotides (GCCGCAGCCC).

      MutationType: plus_1_frameshift_variant; duplication

      CivicName: p.Y98Afs (c.282_291dup)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:endolymphaticsactumor DiseaseEntity:vertigo DiseaseEntity:headache AgeOfPresentation:hemangioblastoma:42 AgeOfPresentation:endolymphaticsactumor:42 AgeOfPresentation:vertigo:42 AgeOfPresentation:headache:42 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:292 ProteinPosition:98 AminoAcidChange:TYRtoALA ClinVarID:N/A MutationType:plus_1_frameshift_variant CivicName:p.Y98Afs(c.282_291dup) NoFamilyInfo CAID:CA2573050500 MutationType:duplication inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4069932/
  11. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Coexistence of VHL Disease and CPT2 Deficiency: A Case Report
    1
    1. ClingenBaseline 30 Oct 2026
      maternal aunts

      PatientID: IV-12

      KindredID: 1

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: The proband (V-5), his mother (IV-8), maternal grandmother (III-6), maternal aunts (IV-10, IV-12), cousin (V-9) and brother (V-6) were found to harbour the VHL mutation p.P86A (c.256 C>G). All were symptomatic of VHL except for his cousin.

      CasePresentingHPOs: HP:0010797, HP:0009711; HP:0001737; HP:0000107; HP:0030405, HP:0030393 (Hemangioblastoma, Retinal capillary hemangioma, Pancreatic cysts, Renal cyst, Pancreatic endocrine tumor, Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 7728151(family 4416); 20375333

      SupplementalData: Information obtained from Figure 1.

      Variant: p.P86A (c.256 C>G)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 93327, https://www.ncbi.nlm.nih.gov/clinvar/variation/93327/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: P86A (c.256C>G)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:endolymphaticsactumor Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:256 ProteinPosition:86 AminoAcidChange:PROtoALA ClinVarID:93327 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:P86A(c.256C>G) Familial FamilyPedigree SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5080814/
  12. Oct 2026
  13. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Characterization of endolymphatic sac tumors and von Hippel–Lindau disease in the International Endolymphatic Sac Tumor Registry
    13
    1. ClingenBaseline 29 Oct 2026
      1 Germany c.236_241delGCAGTC p.Arg79_Ser80del

      GroupID: 4

      Case: Sex unknown, Age unknown, German

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R79_S80del (c.236_241delGCAGTC)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA645524744 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.236_241delGCAGTC

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: inframe_deletion

      CivicName: R79_S80del (c.236_241delGCAGTC)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:236 ProteinPosition:79 CivicName:R79_S80del(c.236_241delGCAGTC) MutationType:inframe_deletion Ethnicity:German ClinVarID:N/A CAID:CA645524744 inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    2. ClingenBaseline 29 Oct 2026
      1 France c.256C>T p.Pro86Ser

      GroupID: 6

      Case: Sex unknown, Age unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86S (c.256C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 178692 https://www.ncbi.nlm.nih.gov/clinvar/variation/178692/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: P86S (c.256C>T)

      MultipleGeneVariants: N/A

      ClinVarID:178692 ClinVarID:Yes Mutation:Germline DiseaseEntity:endolymphaticsactumor DiseaseEntity:VHL RefSeq:NM_000551.3 ProteinPosition:86 CivicName:P86S(c.256C>T) cDNAposition:256 AminoAcidChange:PROtoSER MutationType:missense_variant;transition Ethnicity:French inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 29 Oct 2026
      4 France delEx3 Germany Italy

      GroupID: 38

      DiseaseAssertion: VHL

      GroupSize: 4

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Countries: France, Germany, Italy

      GroupAgeRange: N/A

      GroupInfo: 4 registrants from France, Germany, and Italy were grouped in this study via the deletion of exon 3

      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: Exon 3 Deletion

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: exon_loss_variant

      CivicName: Exon 3 Deletion

      MultipleGeneVariants: N/A

      CivicName:Exon3Deletion MutationType:exon_loss_variant MutationType:deletion CAID:N/A ClinVarID:N/A UnregisteredVariant Mutation:Germline RefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Ethnicity:German Ethnicity:Italian Ethnicity:French inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    4. ClingenBaseline 28 Oct 2026
      1 France c.500G>C p.Arg167Pro

      GroupID: 30

      Case: Sex, Age, Ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. One registrant from France has this mutation of c.500G>C

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167P (c.500G>C)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 428799 https://www.ncbi.nlm.nih.gov/clinvar/variation/428799/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: R167P (c.500G>C)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:500 ProteinPosition:167 AminoAcidChange:ARGtoPRO CivicName:R167P(c.500G>C) CAID:CA351756177 ClinVarID:428799 ClinVarID:Yes MutationType:missense_variant;transversion inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    5. ClingenBaseline 26 Oct 2026
      4 France c.500G>A p.Arg167Gln Italy

      GroupID: 29

      DiseaseAssertion: VHL

      GroupSize: 4

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Four registrants from France or Italy have the same mutation of c.500G>A

      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: p.R167Q (c.500G>A)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167Q (c.500G>A)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:500 ProteinPosition:167 AminoAcidChange:ARGtoGLN CivicName:R167Q(c.500G>A) MutationType:missense_variant;transition CAID:CA020454 ClinVarID:2216 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    6. ClingenBaseline 24 Oct 2026
      1 Germany c.339delA p.Gly114Valfs*45

      GroupID: 13

      Case: Sex unknown, Age unknown, German

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G114Vfs*45 (c.339delA)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA645509026 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.339delA

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: minus_1_frameshift_variant

      CivicName: G114Vfs*45 (c.339delA)

      MultipleGeneVariants: N/A

      Ethnicity:Germany Mutation:Germline RefSeq:NM_000551.3 DiseaseEntity:endolymphaticsactumor DiseaseEntity:VHL ClinVarID:N/A CAID:CA645509026 cDNAposition:339 ProteinPosition:114 AminoAcidChange:GLYtoVAL CivicName:G114Vfs*45(c.339delA) MutationType:minus_1_frameshift_variant inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    7. ClingenBaseline 24 Oct 2026
      1 France c.473T>C p.Leu158Pro

      GroupID: 23

      Case: Sex, Age, Ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant from France was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.L158P (c.473T>C)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 182980 https://www.ncbi.nlm.nih.gov/clinvar/variation/182980/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: L158P (c.473T>C)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:473 ProteinPosition:158 AminoAcidChange:LEUtoPRO CAID:CA020399 ClinVarID:182980 CivicName:L158P(c.473T>C) MutationType:missense_variant;transition ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    8. ClingenBaseline 23 Oct 2026
      1 France c.337C>T p.Arg113*

      GroupID: 12

      Case: Sex, Age, Ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant from France was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R113* (c.337C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R113* (c.337C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:337 ProteinPosition:113 AminoAcidChange:ARGtoTER CivicName:R113*(c.337C>T) MutationType:stop_gained CAID:CA348491 ClinVarID:220414 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    9. ClingenBaseline 22 Oct 2026
      2 Germany c.463+2T>C splice

      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

      ClinVarID:569414 ClinVarID:Yes DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline Ethnicity:German RefSeq:NM_000551.3 cDNAposition:463 CivicName:SpliceSite(c.463+2T>C) MutationType:splice_site_variant inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    10. ClingenBaseline 21 Oct 2026
      1 Italy c.358A>G p.Arg120Gly

      GroupID: 15

      Case: Sex unknown, Age unknown, Italian

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R120G (c.358A>G)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223199 https://www.ncbi.nlm.nih.gov/clinvar/variation/223199/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R120G (c.358A>G)

      MultipleGeneVariants: N/A

      AminoAcidChange:ARGtoGLY ProteinPosition:120 cDNAposition:358 MutationType:missense_variant;transition CivicName:R120G(c.358A>G) ClinVarID:223199 EvidenceStatement Ethnicity:Italian Mutation:Germline DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor RefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    11. ClingenBaseline 21 Oct 2026
      2 France c.486C>G p.Cys162Trp

      GroupID: 26

      DiseaseAssertion: VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: French

      GroupAgeRange: N/A

      GroupInfo: 2 registrants from France were grouped in this study via the mutation of c.486C>G

      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: p.C162W (c.486C>G)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223227 https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: C162W (c.486C>G)

      MultipleGeneVariants: N/A

      ClinVarID:223227 ClinVarID:Yes CivicName:C162W(c.486C>G) cDNAposition:486 ProteinPosition:162 AminoAcidChange:CYStoTRP MutationType:missense_variant;transversion DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Ethnicity:French RefSeq:NM_000551.3 Mutation:Germline inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    12. ClingenBaseline 21 Oct 2026
      2 France c.583C>T p.Gln195*

      GroupID: 35

      DiseaseAssertion: VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Two registrants from France both have the same mutation of c.583C>T.

      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: p.Q195* (c.583C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 428794 https://www.ncbi.nlm.nih.gov/clinvar/variation/428794/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q195* (c.583C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 cDNAposition:583 ProteinPosition:195 AminoAcidChange:GLNtoTER ClinVarID:428794 CAID:CA70052558 MutationType:stop_gained CivicName:Q195*(c.583C>T) ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    13. ClingenBaseline 21 Oct 2026
      3 France c.481C>T p.Arg161* Argentina

      GroupID: 24

      DiseaseAssertion: VHL

      GroupSize: 3

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Three registrants from either France or Argentina have the same mutation of c.481C>T.

      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: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor Mutation:Germline RefSeq:NM_000551.3 ProteinPosition:161 cDNAposition:481 AminoAcidChange:ARGtoTER MutationType:stop_gained CivicName:R161*(c.481C>T) CAID:CA020399 ClinVarID:2217 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/full/10.1002/hed.24067
  14. cancerres.aacrjournals.org cancerres.aacrjournals.org
    Telomere Shortening Is Associated with Genetic Anticipation in Chinese Von Hippel–Lindau Disease Families
    1
    1. ClingenBaseline 29 Oct 2026
      c.481C>T p.Arg161Stop

      PatientID: None (proband 15)

      KindredID: 15

      Case: M, 36Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: Father had died before diagnosis therefore no DNA sample available; He presented with CNS hemangioblastomas at the age of 42.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001737; HP:0009715; HP:0030393 (hemangioblastoma, renal cell carcinoma, pancreatic cysts, papillary cystadenoma of the epididymis, endolymphatic sac tumor)

      CaseHPOFreeText: Patient presented with hemangioblastoma at age 29, renal cell carcinoma at age 29, pancreatic cysts at age 36, endolymphatic sac tumor at age 33, papillary cystadenoma of the epididymis at age 29.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:papillarycystadenomaoftheepididymis DiseaseEntity:endolymphaticsactumor AgeOfPresentation:hemangioblastoma:29 AgeOfPresentation:renalcellcarcinoma:29 AgeOfPresentation:endolymphaticsactumor:33 AgeOfPresentation:papillarycystadenomaoftheepididymis:29 Mutation:Germline AssumedRefSeq:NM_000551.3 ClinVarID:2217 ClinVarID:Yes AminoAcidChange:ARGtoTER MutationType:stop_gained AgeOfPresentation:pancreaticcysts:36 ExperimentalAssay Familial CivicName:R161*(c.481C>T) cDNAposition:481 ProteinPosition:161 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    cancerres.aacrjournals.org/content/74/14/3802
  15. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Endolymphatic sac tumor with von Hippel-Lindau disease: report of a case with analysis of von Hippel-Lindau gene and review
    1
    1. ClingenBaseline 29 Oct 2026
      Herein, we reported a case of ELST with VHL gene analysis who presented with a family history of VHL disease. The radiologic, histologic, and immunohistochemical features of the tumor were typical of ELST.

      PatientID: 1 (case)

      KindredID: 1

      Case: F, 33Y0M, Ethnicity Unknown

      DiseaseAssertion: endolymphatic sac tumor

      FamilyInfo: Her mother and elder sister had history of resection of cerebellar hemangioblastomas, although no genetic testing was done for them.

      CasePresentingHPOs: HP:0030393 (endolymphatic sac tumor)

      CaseHPOFreeText: Woman had progressive hearing disturbance, vertigo, and headache since 32Y. MRI revealed a 4.5 × 3.8 × 3.5-cm mass was detected in the right cerebellopontine angle, destroying the cerebellum. CT with a bone window mode demonstrated extensive destruction of the petrous bone and middle ear structures (endolymphatic sac tumor). The patient underwent craniotomy for a complete removal of the tumor. To date of publication, the patient remains well, with no evidence of recurrent tumor.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: c.340+1G>A

      LegacyVariant: 553 + 1G→A, designated as IVS1 + 1G→A mutation

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223190 https://www.ncbi.nlm.nih.gov/clinvar/variation/223190/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: No LOH was found in this sample

      MutationType: splice_site_variant

      CivicName: Splice site (c.340+1G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:endolymphaticsactumor Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:340 CivicName:SpliceSite(c.340+1G>A) MutationType:splice_site_variant ClinVarID:223190 ClinVarID:Yes Familial AgeOfPresentation:endolymphaticsactumor:32 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/20850701/
  16. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Genotype-phenotype correlation in paediatric pheochromocytoma and paraganglioma: a single centre experience from India
    1
    1. ClingenBaseline 28 Oct 2026

      PatientID: None

      KindredID: 3

      Case: F, 20Y0M, Ethnicity unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: Familial/syndromic (FS) association

      CasePresentingHPOs: HP:0002666; HP:0030393; HP:0030405; HP:0001737; HP:0000107 (Pheochromocytoma; endolymphatic sac tumor; pancreatic endocrine tumor; pancreatic cysts; renal cyst)

      CaseHPOFreeText: Benign unilateral pheochromocytoma at age 20Y0M; as well as ELST, PNETs, pancreatic and renal cysts

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: SDHB,SDHC, SDHD, and exons 10, 11, 13, 14, 15 and 16 of RET proto-oncogene

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: Deletion of exon 1

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Heterozygous deletion of exon 1

      MutationType: exon_loss_variant

      CivicName: Exon 1 Deletion

      MultipleGeneVariants: N/A

      UnregisteredVariant ClinVarID:N/A InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:20 DiseaseEntity:endolymphaticsactumor DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst Mutation:Germline AssumedRefSeq:NM_000551.3 MutationType:exon_loss_variant CivicName:Exon1Deletion Familial PreviousTesting:RET/SDHB/SDHC/SDHD inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/28432847/
  17. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Clinical and molecular characterization of Brazilian families with von Hippel-Lindau disease: a need for delineating genotype-phenotype correlation
    1
    1. ClingenBaseline 26 Oct 2026
      PMID: 20567917

      PatientID: 2

      KindredID: 2

      Case: F, 29Y0M, Brazilian

      DiseaseAssertion: VHL

      FamilyInfo: VHL type 1. Genetic testing has been performed in her parents and brother with negative results. Her only child has not undergone predictive testing yet.

      CasePresentingHPOs: HP:0030393; HP:0009711; HP:0010797; HP:0000107; HP:0001737; HP:0001407 (endolymphatic sac tumor; retinal capillary hemangioma; hemangioblastoma; renal cysts; pancreatic cysts; hepatic cysts)

      CaseHPOFreeText: endolymphatic sac tumor diagnosed at 11Y, retinal angiomas at 16Y; hemangioblastoma, renal, pancreatic, and hepatic cysts at 29Y

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes

      Variant: p.Q73* (c.217C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Brazilian DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hepaticcysts DiseaseEntity:renalcyst DiseaseEntity:pancreaticcysts DiseaseEntity:hemangioblastoma AgeOfPresentation:endolymphaticsactumor:11 AgeOfPresentation:retinalcapillaryhemangioma:16 AgeOfPresentation:hemangioblastoma:29 AgeOfPresentation:hepaticcysts:29 AgeOfPresentation:pancreaticcysts:29 Mutation:Germline RefSeq:NM_000551.2 NonFamilial FamilyPedigree ClinVarID:223164 ClinVarID:Yes MutationType:stop_gained ProteinPosition:73 cDNAposition:217 CivicName:Q73*(c.217C>T) AminoAcidChange:GLNtoTER SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/20567917/
  18. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    A c.464T>a mutation in VHL gene in a Chinese family with VHL syndrome
    1
    1. ClingenBaseline 24 Oct 2026
      Von Hippel-Lindau (VHL) is a tumor suppressor that negatively regulates the production of angiogenic factors. Mutations in the VHL gene cause VHL syndrome, which is characterized by highly vascularized tumors. Here we report a c.464T>A mutation of the VHL gene in three patients with hemangioblastoma from a Chinese family. This mutation was not reported previously and was absent in the unaffected family members. The mutation is predicted to cause Val to Glu substitution at VHL protein residue 155 in a conserved region. Previous biochemical studies demonstrated that residue Val-155 was critical for VHL protein binding to chaperonin TRiC/CCT, an essential step for proper VHL protein folding. Our finding of naturally occurring VHL V155E mutation in patients with VHL syndrome supports the functional importance of Val-155 residue in VHL protein and illustrates the diversity of VHL gene defects underlying VHL syndrome.

      PatientID: III-1

      KindredID: 1

      Case: F, 26Y0M, Chinese

      DiseaseAssertion: assumed VHL

      FamilyInfo: 10 members of this Chinese family were tested, and 3 were found with the same genetic mutation (c.464T>A). The proband’s grandmother (I-1, 79Y), and father (II-1, 53Y) had hemangioblastomas, and tested positive for the mutation. This mutation was not found in the other unaffected members in the family.

      CasePresentingHPOs: HP:0006880; HP:0030405; HP:0002666 (cerebellar hemangioblastoma, endolyphmatic sac tumor, pheochromocytoma)

      CaseHPOFreeText: patient suffered with dizziness and headache and frequent vomiting since 25Y (CT and MRI identified occupying lesions and obstructive hydrocephalus in the cerebellar vermis). The cerebellar tumor nodes were removed surgically. Abdominal CT showed multiple lesions in the liver, pancreas and posterior peritoneum. The tumors in the proband’s pancreatic tail and retroperitoneal space also were removed subsequently. Histological analysis indicated the tumors to be pancreatic isletcell tumor and phaeochromocytoma, respectively.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: patient was negative in the bilateral Babinski’s sign test

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V155E (c.464T>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351756032 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.464T%3EA

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V155E (c.464T>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:endolymphaticsactumor DiseaseEntity:pheochromocytoma CivicName:V155E(c.464T>A) cDNAposition:464 AminoAcidChange:VALtoGLU ProteinPosition:155 MutationType:missense_variant;transversion CAID:CA351756032 ClinVarID:N/A Familial FamilyPedigree ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/23203444/
  19. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Alu-Alu recombination underlies the vast majority of large VHL germline deletions: Molecular characterization and genotype-phenotype correlations in VHL patients
    2
    1. ClingenBaseline 24 Oct 2026
      We identified deletions ranging from 0.5 kb to 250 kb affecting part of or the entire VHL and flanking genes in 54 families.

      GroupID: 43

      DiseaseAssertion: VHL

      GroupSize: N/A GroupNumberMales: N/A GroupNumberFemales: N/A GroupEthnicity: N/A GroupAgeRange: N/A

      GroupInfo: 54 VHL deletion families from the Freiburg registry were selected in order to assist in the correlation of VHL deletions to clinical phenotypes.

      GroupPresentingHPOs: HP:0005584; HP:0000107; HP:0009711; HP:0010797; HP:0030393; HP:0001737; HP:0030405 (Renal cell carcinoma, Renal cyst, Retinal capillary hemangioma, Hemangioblastoma, Endolymphatic sac tumor, Pancreatic cysts, Pancreatic endocrine tumor)

      GroupHPOFreeText: # of affected individuals: Renal cell carcinoma (1), Renal cyst (2), Retinal capillary hemangioma (4), Hemangioblastoma/brain/cerebellum (3), Endolymphatic sac tumor (2), Pancreatic cysts (3), Pancreatic endocrine tumor (1)

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplemental Table 2, Table 1, Table 3

      Variant: Exon 1-3 Deletion (c.1-?_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: Exon 1-3 Deletion

      MultipleGeneVariants: Germline, IRAK2, partial deletion

      MultipleGeneVariants: Germline, ENST197804, partial deletion

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:renalcyst DiseaseEntity:hemangioblastoma DiseaseEntity:pancreaticcysts DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:endolymphaticsactumor DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:renalcellcarcinoma Mutation:Germline RefSeq:NM_000551.2 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant CivicName:Exon1-3Deletion Familial FamilyCohort MultipleGeneVariants SupplementalData UnregisteredVariant inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 22 Oct 2026
      We identified deletions ranging from 0.5 kb to 250 kb affecting part of or the entire VHL and flanking genes in 54 families

      GroupID: 2

      DiseaseAssertion: VHL

      GroupSize: N/A GroupNumberMales: N/A GroupNumberFemales: N/A GroupEthnicity: N/A GroupAgeRange: N/A

      GroupInfo: 54 VHL deletion families from the Freiburg registry were selected in order to assist in the correlation of VHL deletions to clinical phenotypes.

      GroupPresentingHPOs: HP:0009711; HP:0009713; HP:0030393; HP:0030424 (Retinal capillary hemangioma, Spinal hemangioblastoma, Endolymphatic sac tumor, Epididymal cyst)

      GroupHPOFreeText: # of affected individuals: Retinal capillary hemangioma (1), Spinal hemangioblastoma (1), Endolymphatic sac tumor (1), Epididymal cyst (1)

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplemental Table 2, Table 1, Table 3

      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: Germline, ENST197804, partial deletion

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:endolymphaticsactumor DiseaseEntity:epididymalcyst Mutation:Germline RefSeq:NM_000551.2 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A MutationType:exon_loss_variant CivicName:Exon1Deletion Familial FamilyCohort MultipleGeneVariants SupplementalData UnregisteredVariant inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/19280651/
  20. www.endocrinepractice.org www.endocrinepractice.org
    VHL-Related Neuroendocrine Neoplasms And Beyond: An Israeli Specialized Center Real-Life Report
    1
    1. ClingenBaseline 23 Oct 2026
      16 different families

      PatientID: 1

      KindredID: 5

      Case: M, 19Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Patient had 3 carrier children of this mutation, without any further phenotypic information.

      CasePresentingHPOs: HP:0005584; HP:0000107; HP:0006748; HP:0009713; HP:0001737; HP:0030939; HP:0100684 (renal cell carcinoma, renal cysts, adrenal pheochromocytoma, spinal hemangioblastoma, pancreatic cysts, endolymphatic sac tumor, salivary gland neoplasm)

      CaseHPOFreeText: Patient presented with renal cell carcinoma, renal cysts, adrenal pheochromocytoma, spinal hemangioblastoma, pancreatic cysts, endolymphatic sac tumor and salivary gland neoplasm at age 19Y0M. Patient was diagnosed with VHL type 1 (see table 2).

      CaseNotHPOs: HP:0002668; HP:0030405 (paraganglioma; pancreatic endocrine tumor)

      CaseNotHPOFreeText: Patient negative for paraganglioma and pancreatic endocrine tumor.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G93R (c.277G>C)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223174, https://www.ncbi.nlm.nih.gov/clinvar/variation/223174

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant, transversion

      CivicName: G93R (c.277G>C)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion RefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:renalcyst DiseaseEntity:renalcellcarcinoma DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:spinalhemangioblastoma DiseaseEntity:pancreaticcysts DiseaseEntity:endolymphaticsactumor DiseaseEntity:salivaryglandneoplasm CivicName:G93R(c.277G>C) cDNAPosition:277 ProteinPosition:93 AminoAcidChange:GLYtoARG ClinVarID:Yes ClinVarID:223174 Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    endocrinepractice.org/article/S1530-891X(20)48218-7/fulltext
  21. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    Frequency of Von Hippel-Lindau germline mutations in classic and non-classic Von Hippel-Lindau disease identified by DNA sequencing, Southern blot analysis and multiplex ligation-dependent probe amplification
    1
    1. ClingenBaseline 23 Oct 2026
      15 c.500G>A p.Arg167Gln p.R167Q Familial VHL

      GroupID/ KindredID: 15

      DiseaseAssertion: VHL

      GroupSize: 5

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Described are 5 patients with this familial VHL mutation. They belong to family 15 and have the germline VHL mutation of c.500G>A.

      GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0005584; HP:0000107; HP:0001737; HP:0002666; HP:0030393 (retinal capillary hemangioma, hemangioblastoma, renal cell carcinoma, renal cyst, pancreatic cysts, pheochromocytoma, endolymphatic sac tumor)

      GroupHPOFreeText: of the totalling 5 members, 3 have rHAB, 3 have cHAB, 3 have renal cysts, 2 have RCC, 2 patients suspected (deafness, tinnitius, or vertigo) for an endolymphatic sac tumor (ELST), 1 has a pheochromocytoma and 1 has a pancreatic cyst. Additionally an adnexal papillary tumor of probable mesonephric origin (APMO) was recorded in this cohort.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: Previously reported, HGMD (Human Gene Mutation Database: http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/120488.html)

      SupplementalData: N/A

      Variant: p.R167Q (c.500G>A)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167Q (c.500G>A)

      MultipleGeneVariants: N/A

      Mutation:Germline RefSeq:NM_000551.2 DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:renalcyst DiseaseEntity:pancreaticcysts DiseaseEntity:pheochromocytoma DiseaseEntity:endolymphaticsactumor ClinVarID:2216 CAID:CA020454 MutationType:missense_variant;transition CivicName:R167Q(c.500G>A) Familial cDNAposition:500 ProteinPosition:167 AminoAcidChange:ARGtoGLN ClinVarID:Yes InheritancePattern:AutosomalDominant ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1111/j.1399-0004.2007.00827.x
  22. journals.lww.com journals.lww.com
    PARS PLANA VITRECTOMY IN ADVANCED CASES OF VON... : RETINA
    1
    1. ClingenBaseline 22 Oct 2026
      detected point germline vhl mutations in 14 patients

      PatientID: 23

      KindredID: 23

      Case: 23Y0M, sex unknown, ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797; HP:0030393; HP:0005584; HP:0009711 (hemangioblastoma; endolymphatic sac tumor; renal cell carcinoma; retinal capillary hemangioma)

      CaseHPOFreeText: See Table 1&2 for retinal capillary hemangioma information

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N78I (c.233A>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223169 https://www.ncbi.nlm.nih.gov/clinvar/variation/223169/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: N78I (c.233A>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:hemangioblastoma DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor DiseaseEntity:renalcellcarcinoma DiseaseEntity:retinalcapillaryhemangioma MutationType:missense_variant;transversion cDNAposition:233 ProteinPosition:78 CivicName:N78I(c.233A>T) AminoAcidChange:ASNtoILE ClinVarID:Yes ClinVarID:223169 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    journals.lww.com/retinajournal/fulltext/2016/02000/pars_plana_vitrectomy_in_advanced_cases_of_von.13.aspx
  23. link.springer.com link.springer.com
    Conservative management of endolymphatic sac tumors in von Hippel–Lindau disease: case report
    2
    1. ClingenBaseline 22 Oct 2026
      Patient 2 The second patient had a familial history of VHL disease but had never been screened for central nervous system manifestations when she experienced a sudden left hearing loss at 18 years old. The MRI revealed a left mass of the temporal bone invading the otic capsule but without extension in the cerebellopontine angle (Fig. 1) and also a cystic hemangioblastoma of the brainstem with significant mass burden but no associated symptoms. It was decided to operate on the hemangioblastoma first due to its size and location and the endolymphatic sac tumor remained under surveillance. The MTD of the endolymphatic sac tumor at diagnosis was 1.9 cm. Apart from central nervous systems hemangioblastomas, the patient developed pancreatic cysts in the course of her VHL disease. The germline mutation of the VHL gene was also identified (c.345C>G, p.His115Gln). During 18 years of surveillance, the tumor increased in size following a two-phase growth pattern alternating phases of quiescence and phases of continuous growth (Fig. 2). Apart from her left cophosis, she did not suffer from any vestibular symptoms and the rest of her neurological exam remained normal. As tumor did not develop in the cerebellopontine angle and did not threaten the brainstem, it was decided to postpone surgery and the patient remains under surveillance.

      PatientID: 2

      KindredID: 2

      Case: F, 36Y0M, Ethnicity Unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: familial history of VHL disease

      CasePresentingHPOs: HP:0030393; HP:0010797; HP:0001737 (endolymphatic sac tumor, hemangioblastoma, pancreatic cysts)

      CaseHPOFreeText: at 18Y experienced a sudden left hearing loss (MRI revealed hemangioblastomas of the temporal bone invading the otic capsule; operated on; the MTD of the endolymphatic sac tumor at diagnosis was 1.9 cm). The patient also developed pancreatic cysts.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.H115Q (c.345C>G)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 496058 https://www.ncbi.nlm.nih.gov/clinvar/variation/496058/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: H115Q (c.345C>G)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL InheritancePattern:AutosomalDominant DiseaseEntity:endolymphaticsactumor DiseaseEntity:hemangioblastoma DiseaseEntity:pancreaticcysts AgeOfPresentation:endolymphaticsactumor:18 AminoAcidChange:HIStoGLN ProteinPosition:115 cDNAposition:345 ClinVarID:496058 ClinVarID:Yes Familial MutationType:missense_variant;transversion CivicName:H115Q(c.345C>G) Mutation:Germline AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 21 Oct 2026
      Patient 1 The first patient had no familial history of VHL disease and was 21 years old when he experienced a sudden right hearing loss. The resulting cophosis was irreversible. The radiological work-up revealed an osteolytic mass of the right temporal bone of heterogeneous signal on both T1- and T2-weighted images (Fig. 1), consistent with the diagnosis of endolymphatic sac tumor. The tumor invaded the otic capsule and the petrous apex but did not extend in the cerebellopontine angle. Its mean tumor diameter (MTD) at diagnosis was approximately 2.6 cm (formula—MTD = (length×width×height)1/3MTD = (length×width×height)1/3 {\hbox{MTD = }}{\left( {{\hbox{length}} \times {\hbox{width}} \times {\hbox{height}}} \right)^{{1/3}}} ) [16]. The rest of the neurological exam was normal and a conservative management was decided. During follow-up, the patient suffered from other manifestations of VHL disease: retinal and central nervous system hemangioblastomas, pheochromocytoma, renal tumors, and pancreatic cysts. The germline mutation of the VHL gene was also identified (c.337C>T, p.Arg113X). After 20 years of radiological surveillance, the size of his endolymphatic sac tumor remains stable (Fig. 2). Apart from his deafness, the patient does not suffer from any vestibular symptoms and his facial function is normal (House and Brackmann grade I).

      PatientID: 1

      KindredID: 1

      Case: M, 41Y0M, Ethnicity Unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: No family history of VHL disease.

      CasePresentingHPOs: HP:0030393; HP:0009711; HP:0010797; HP:0002666; HP:0009726; HP:0001737 (endolymphatic sac tumor, retinal capillary hemangioma, hemangioblastoma, pheochromocytoma, renal neoplasm, pancreatic cysts)

      CaseHPOFreeText: patient was 21 years old when he experienced a sudden right hearing loss (cophosis). During a follow-up, the patient suffered from other manifestations of VHL disease mentioned above.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R113* (c.337C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R113*(c.337C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:pheochromocytoma DiseaseEntity:renalneoplasm DiseaseEntity:pancreaticcysts AgeOfPresentation:endolymphaticsactumor:21 Mutation:Germline AssumedRefSeq:NM_000551.3 ClinVarID:220414 ClinVarID:Yes ProteinPosition:113 CivicName:R113*(c.337C>T) cDNAposition:337 AminoAcidChange:ARGtoTER MutationType:stop_gained NonFamilial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    link.springer.com/article/10.1007/s00701-010-0873-5