5 Matching Annotations
  1. Last 7 days
  2. www.tandfonline.com www.tandfonline.com
    Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene
    3
    1. ClingenBaseline 03 Nov 2026
      The stop codon mutation c.481C>T, p.Arg161* (known as: c.694C>T, p.Arg232* according to the former nomenclature), also situated in exon 3 of the gene, was detected in a 46-year-old male (patient #4) self-referred and presenting (as reported by himself) two RCC and two cHB. Several family members were affected by the VHL disease: the patient's father has been operated for multiple large cHBs; the patient's brother has been operated for multiple cHBs and died from RCC; his nephew (brother's son) has been operated for large cHB. Unfortunately, the patient did not provide us with more detailed medical data on his own condition.

      PatientID: 4

      KindredID: 4

      Case: M, 46Y0M, Bulgarian

      DiseaseAssertion: VHL

      FamilyInfo: Several family members were affected by the VHL disease: the patient's father has been operated for multiple large cHBs; the patient's brother has been operated for multiple cHBs and died from RCC; his nephew (brother's son) has been operated for large cHB. No familial genotype was confirmed.

      CasePresentingHPOs: HP:0005584; HP:0010797 (renal cell carcinoma, hemangioblastoma)

      CaseHPOFreeText: 2 RCC and 2 cHB were both self-reported; patient was operated and treated for RCC; follow-up for cHB.

      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: SNP c.870A>G in CCND1 gene (G>G)

      InheritancePattern:AutosomalDominant Ethnicity:Bulgarian DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:hemangioblastoma Mutation:Germline RefSeq:NM_000551.3 CivicName:R161*(c.481C>T) cDNAposition:481 AminoAcidChange:ARGtoTER MutationType:stop_gained ClinVarID:2217 ClinVarID:Yes Familial ProteinPosition:161 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 01 Nov 2026
      The missense mutation c.332G>A, p.Ser111Asn in VHL exon 1 was detected in a 60-year-old female (patient #5) affected by cHB, bilateral renal and pancreatic cysts and RCC (VHL type 1).

      PatientID: 5

      KindredID: 5

      Case: F, 60Y0M, Bulgarian

      DiseaseAssertion: VHL

      FamilyInfo: Positive family history for VHL - daughter and grandson; no genotype confirmed.

      CasePresentingHPOs: HP:0010797; HP:0001737; HP:0000107; HP:0005584 (hemangioblastoma; pancreatic cysts; renal cyst; renal cell carcinoma)

      CaseHPOFreeText: retinal capillary hemangioma and RCC were operated on. Bilateral renal and pancreatic cysts were also recorded

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

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

      LegacyVariant: N/A

      CaseProblemVariantFreeText: 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: SNP c.870A>G in CCND1 gene (G>G)

      InheritancePattern:AutosomalDominant Ethnicity:Bulgarian DiseaseEntity:hemangioblastoma DiseaseEntity:renalcyst DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts Mutation:Germline RefSeq:NM_000551.3 Familial ClinVarID:223186 ClinVarID:Yes CivicName:S111N(c.332G>A) cDNAposition:332 MutationType:missense_variant;transition ProteinPosition:111 AminoAcidChange:SERtoASN inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 30 Oct 2026
      The novel CME combines a duplication and an indel, rearranging exon 3 of the VHL gene-c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4) (Figure 2). This genetic rearrangement was detected in a 27-year-old female (patient #3) with an infratentorial tumour, initially considered on MRI to be ependymoma or haemangiopericytoma, but having the typical characteristics of cHB (Figure 3). After operation, HB of the cerebellum was histologically proven. Family history revealed that the patient's father has been operated for cHB and rHB, but unfortunately, the family has never been informed that the father's condition is VHL, which is an inheritable disease, and that the offspring should undergo regular screening by MRI of CNS beginning in adolescence [9Maher ER, Neumann HP, Richard S. Von Hippel-Lindau disease: a clinical and scientific review. Eur J Hum Genet. 2011;19(6):617–623. [Crossref], [PubMed], [Web of Science ®], [Google Scholar],22Shuin T, Yamasaki I, Tamura K, et al. Von Hippel-Lindau disease: molecular pathological basis, clinical criteria, genetic testing, clinical features of tumors and treatment. Jpn J Clin Oncol. 2006;36:337–343. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. The index patient might be classified as having the so called ‘type 1 VHL’ (rHB and cHB but at a low risk of RCC), which is related to contiguous deletion of all or part of VHL [9Maher ER, Neumann HP, Richard S. Von Hippel-Lindau disease: a clinical and scientific review. Eur J Hum Genet. 2011;19(6):617–623. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. Unfortunately, the father was not available for performing molecular genetic testing.

      PatientID: 3

      KindredID: 3

      Case: F, 27Y0M, Bulgarian

      DiseaseAssertion: VHL

      FamilyInfo: Positive family history of retinal HB and CNS HB - father was operated on for both; he was not available for performing molecular genetic testing thus no genotype was confirmed.

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

      CaseHPOFreeText: retinal capillary hemangioma was found in this patient; and an infratentorial tumour, initially considered on MRI to be ependymoma or haemangiopericytoma, but having the typical characteristics of cHB - after operation, HB of the cerebellum was histologically proven.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.E173Sfs*4 (c.516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: A duplication and deletion-insertion are both involved in this protein change.

      ClinVarID: N/A

      CAID: Two CAIDs are associated with the cDNA changes, just note that together they result in one protein change, which is not registered. - CA2499306821 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499306821 (c.516_517dupGTCAAGCCT) - CA2499306820 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499306820 (c.532_542delCTGGACATCGTinsATTA) - p.E173Sfs4 NOT* registered with associating p.s

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: duplication AND delins

      CivicName: c.516_517dupGTCAAGCCT and c.532_542delCTGGACATCGTinsATTA

      MultipleGeneVariants: SNP c.870A>G in CCND1 gene (A>G)

      InheritancePattern:AutosomalDominant Ethnicity:Bulgarian DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma cDNAposition:516 cDNAposition:532 ProteinPosition:173 AminoAcidChange:GLUtoSER Mutation:Germline RefSeq:NM_000551.3 MutationType:duplication MutationType:delins MultipleGeneVariants Familial ClinVarID:N/A UnregisteredVariant CAID:CA2499306820 CAID:CA2499306821 CAID:N/A CivicName:c.516_517dupGTCAAGCCTandc.532_542delCTGGACATCGTinsATTA inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    tandfonline.com/doi/full/10.1080/00207454.2017.1372436
  3. Oct 2026
  4. www.tandfonline.com www.tandfonline.com
    Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene
    2
    1. ClingenBaseline 25 Oct 2026
      The exon 1 deletion c.254_283del30, p.Leu85_Glu94del was detected in a girl (patient #1) with manifestation of bilateral rHB and single vertebral HB at the age of 14 years (VHL type 1).

      PatientID: 1

      KindredID: 1

      Case: F, 14Y0M, Bulgarian

      DiseaseAssertion: VHL

      FamilyInfo: Negative family history for VHL

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

      CaseHPOFreeText: retinal capillary hemangioma and a single vertebral hemangioblastoma (at C6) were found; follow up showed bilateral retinal hemangioma (operated on)

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.L85_E94del (c.254_283del30bp)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA2499306645 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499306645

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: inframe_deletion

      CivicName: L85_E94del (c.254_283del30bp)

      MultipleGeneVariants: SNP c.870A>G in CCND1 gene (A>G)

      Ethnicity:Bulgarian DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:hemangioblastoma:14 DiseaseEntity:hemangioblastoma AgeOfPresentation:retinalcapillaryhemangioma:14 Mutation:Germline DiseaseEntity:VHL RefSeq:NM_000551.3 CAID:CA2499306645 ClinVarID:N/A NonFamilial MutationType:inframe_deletion cDNAposition:254 CivicName:L85_E94del(c.254_283del30bp) ProteinPosition:85 inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    2. ClingenBaseline 21 Oct 2026
      The missense mutation p.Arg167Gln in VHL exon 3 was detected in an index female (patient #2) and her mother

      PatientID: None

      KindredID: 2

      Case: F, Age unknown, Bulgarian

      DiseaseAssertion: VHL

      FamilyInfo: Patient has a daughter (PatientID: 1) with bilateral pheo and retinal hemangioma as well.

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

      CaseHPOFreeText: bilateral pheochromocytoma

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

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

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

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

      CAID: N/A

      gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

      VariantEvidence:N/A

      MutationType: missense_variant;transition

      CivicName: R167Q (c.500G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Bulgarian DiseaseEntity:pheochromocytoma DiseaseEntity:retinalcapillaryhemangioma Mutation:Germline RefSeq:NM_000551.3 CivicName:R167Q(c.500G>A) cDNAposition:500 ProteinPosition:167 AminoAcidChange:ARGtoGLN ClinVarID:2216 ClinVarID:Yes MutationType:missense_variant;transition Familial DiseaseEntity:VHL inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    tandfonline.com/doi/full/10.1080/00207454.2017.1372436