4 Matching Annotations
  1. Last 7 days
  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Management of Gene Variants of Unknown Significance: Analysis Method and Risk Assessment of the VHL Mutation p.P81S (c.241C>T)
    1
    1. ClingenBaseline 02 Nov 2026
      along with a silent mutation p.P2P (c.6C>G) in the VHL gene

      PatientID: None

      KindredID: 1

      Case: M, 31Y0M, Danish

      DiseaseAssertion: VHL

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

      CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

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

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

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

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

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

      CAID: N/A

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

      VariantEvidence: N/A

      MutationType: synonymous_variant

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

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

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Ethnicity:Danish AssumedRefSeq:NM_000551.3 Familial FamilyPedigree AgeOfPresentation:renalcellcarcinoma:29 DiseaseEntity:renalcellcarcinoma ClinVarID:456593 ClinVarID:Yes MultipleVHLVariants MutationType:synonymous_variant cDNAposition:6 AminoAcidChange:PROtoPRO ProteinPosition:2 CivicName:P2=(c.6C>G)andP81S(c.241C>T) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5321774/
  3. Oct 2026
  4. www.sciencedirect.com www.sciencedirect.com
    Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene
    1
    1. ClingenBaseline 25 Oct 2026
      Case 3 (intradural tumor of T7 spinal nerve roots), which was first thought to be sporadic (non-familial) in 2001, was then re-classified as “HB-only VHLD” (form fruste of VHLD) after the patient’s sister, aged 53, was diagnosed with cerebellar HB (in the sister a germline point mutation and 2 somatic point mutations were found in the DNA of the cerebellar HB, and the case was included as case HB-25 in another study [28]). To the best of our knowledge, this is the first case of a patient with “HB-only VHLD” having clinical expression outside CNS.

      PatientID: N/A

      KindredID: 3

      Case: F, 53Y0M, Italian

      DiseaseAssertion: VHL

      FamilyInfo: Sister was thought to be sporadic (non familial) in 2001 with a spinal T7 tumor - genetic testing in this paper describes her (the sister, case 3) without any mutations.

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: The patient had a single cerebellar hemangioblastoma that was diagnosed at age 53. She had a germline point and 2 somatic point mutations found in the DNA of her CHB. These mutations are discussed further in PMID: 24335534

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 24335534 (pt. HGB-25)

      SupplementalData: Supplemental Digital Content 1. Primer Sequences for VHL gene amplification, LOH and methylation analysis.

      Variant: p.D126Rfs*6 (c.375_376insA)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA2573320316 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2573320316

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: plus_1_frameshift_variant

      CivicName: P25L(c.74C>T) and D126Rfs*6(c.375_376insA) and E55Rfs(c.163delG)

      MultipleGeneVariants: Somatic, VHL, c.163delG (p.Glu55Argfs), Germline, VHL, c.74C>T (p.Pro25Leu)

      InheritancePattern:AutosomalDominant Mutation:Somatic Familial Ethnicity:Italian DiseaseEntity:VHL AgeOfPresentation:cerebellarhemangioblastoma:53 DiseaseEntity:cerebellarhemangioblastoma MultipleVHLVariants CAID:CA2573320316 ClinVarID:N/A MutationType:plus_1_frameshift_variant CivicName:P25L(c.74C>T)andD126Rfs*6(c.375_376insA)andE55Rfs(c.163delG) AminoAcidChange:ASPtoARG cDNAposition:375 ProteinPosition:126 AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    sciencedirect.com/science/article/pii/S0344033818303327
  5. www-sciencedirect-com.proxy1.lib.uwo.ca www-sciencedirect-com.proxy1.lib.uwo.ca
    Pars plana vitrectomy for juxtapapillary capillary retinal angioma
    1
    1. ClingenBaseline 25 Oct 2026
      6-year-old otherwise healthy girl

      PatientID: None

      KindredID: 1

      Case: F, 6Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Family history revealed VHL in the father and grandfather. Molecular genetic analysis confirmed familial VHL by detecting a mutation of the VHL gene in the patient, her father, and her sister. Magnetic resonance imaging revealed spinal hemangioblastomas and kidney cysts in the father, but not in the patient.

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: The patient had symptomatic juxtapapillary capillary retinal angioma with associated epiretinal membrane (ERM). Pars Plana Vitrectomy and removal of ERM resulted in substantial improvement of vision.

      CaseNotHPOs: HP:0009713, HP:0000107( Spinal Hemangioblastoma, Renal Cyst)

      CaseNotHPOFreeText: Magnetic resonance imaging revealed spinal hemangioblastomas and kidney cysts in the father, but not in the patient.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.S65W (c.194C>G)

      LegacyVariant: (407C>G)

      CaseProblemVariantFreeText: N/A

      ClinVar: 43597 https://www.ncbi.nlm.nih.gov/clinvar/variation/43597/

      CAID: CA020099 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA020099

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: S65W (c.194C>G)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:6 Mutation:Germline MutationType:missense_variant;transversion cDNAposition:194 ProteinPosition:65 AminoAcidChange:SERtoTRP ClinVarID:43597 CAiD:CA020099 CivicName:S65W(c.194C>G) Familial DiseaseEntity:VHL AssumedRefSeq:AF010238.1 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    www-sciencedirect-com.proxy1.lib.uwo.ca/science/article/pii/S0002939405010913
  6. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    Diagnosis at dusk: Malignant hypertension and phaeochromocytoma in a 6-year-old girl
    1
    1. ClingenBaseline 24 Oct 2026
      Case report A 6-year-old girl was brought into the ED by her parents in the late evening with a 5 week history of colicky, peri-umbilical pain and general malaise. Her mother reported that they had been to the family doctor repeatedly since the onset of symptoms and trialled a number of medications (including antispasmodics and various analgesics) without success. On further questioning, the patient described several episodes of spontaneous vomiting without obvious cause or association over the past month. Her appetite was poor and she had been losing weight. There were no other gastrointestinal or urinary symptoms. There was no history of fever, although she did report ‘sweating for no reason’ on occasion. She had also been suffering from intermittent, generalized headaches without any other focal symptoms over the same time period. She had been previously well, the only noteworthy point in her medical history being her conception through in vitro fertilization. There were no developmental concerns or family history of note. On examination, the patient appeared pale, tired, mildly dehydrated, but apyrexial and comfortable at rest. She was profoundly tachycardic, with a heart rate of 170 beats per minute, and had a BP of 203/157 mmHg on repeat measurements (normal systolic range 90–110 mmHg in this age group). Crucially, as the patient arrived in the early evening, she was triaged in the adult ED and not the paediatric ED (which was closed at this time), where BP would not have been part of routine observations in this age group. Urinary dipstick showed raised protein and blood. General examination was otherwise normal. In discussion with paediatric cardiology, the patient was started immediately on oral nifedipine to control the malignant hypertension prior to further investigation. Blood tests revealed low potassium of 3.0 mmol/L (normal 3.3–4.6) with raised urea (10.0 mmol/L; 2.5–6.5) and creatinine (81 mmol/L; 25–60). Routine haematology and biochemistry bloods (including liver and thyroid function tests) were otherwise unremarkable. An abdominal ultrasound scan demonstrated a 3 × 2.5 cm mass at the upper pole of the left kidney without a distinctly identifiable adrenal gland, a finding confirmed on CT (Fig. 1), which also showed some low attenuation suggestive of cystic change within the mass. Serial urinary metanephrines were subsequently found to be grossly elevated (17.0, 18.1 and 14.7 µmol/mmol creatinine; normal <1.74) with a predominant normetanephrine fraction, suggesting a diagnosis of phaeochromocytoma. Figure 1Open in figure viewerPowerPoint Ultrasound image (above) of the patient's left kidney (between the two crosses) clearly showing an abnormal mass associated with the organ. The adrenal cannot be distinctly identified. The mass was further characterized on CT (below, the mass having been circled). Sympathetic blockade was established first using gradually increasing doses of oral phenoxybenzamine (switched to i.v. dosing in the 5 days prior to surgery), then adding propranolol, aiming for a systolic BP of 80 mmHg with postural drop of 10 mmHg in order to facilitate safe removal of the tumour. Concurrent investigations identified raised serum renin and aldosterone levels consistent with secondary hyperaldosteronism. Serum calcitonin and urinary steroid profiles were normal, as was retinal screening for abnormalities associated with von Hippel-Lindau (vHL) disease, including retinal haemangiomas and hypertensive retinopathy. A laparoscopic left adrenalectomy took place 6 weeks after initial presentation, and priority was placed on close cardiovascular monitoring perioperatively. The patient was fit for discharge 3 days after surgery histology subsequently confirming the diagnosis of phaeochromocytoma.

      PatientID: 1

      KindredID: 1

      Case: F, 6Y0M, Ethnicity Unknown

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: No history - the only noteworthy point in her medical history being her conception through in vitro fertilization, however no noted concerns. This mutation was not present in either parent, indicating a de novo.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: patient presented with a prolonged history of general malaise, headaches and abdominal pain. She was noted to have malignant hypertension. Subsequent imaging of the abdomen demonstrated a left adrenal mass (diagnosis of phaeochromocytoma confirmed by serial raised urinary metanephrines). Sympathetic blockade was established prior to definitive surgical treatment, resulting in complete resolution of the patient’s symptoms and hypertension.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N90H (c.268A>C)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351750708 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.268A%3EC

      gnomAD: N/A

      VariantEvidence: Neurofibromatosis type (NF) 1 was excluded on clinical grounds as she had none of the cutaneous features. Mutational analysis of the RET proto-oncogene was normal, making MEN2 unlikely. Sequencing of exons 1–3 of the VHL gene revealed a novel single base pair substitution (A268C).

      MutationType: missense_variant;transversion

      CivicName: N90H (c.268A>C)

      MultipleGeneVariants: N/A

      DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:6 InheritancePattern:DeNovoAssertion deNovoConfirmed Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:268 MutationType:missense_variant;transversion ProteinPosition:90 AminoAcidChange:ASNtoHIS CivicName:N90H(c.268A>C) CAID:CA351750708 ClinVarID:N/A 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.1742-6723.2007.01049.x