553 G/A
A retrospective study described polyglobulia in 19 patients precise germline VHL mutations and with hemangioblastomas. 10 other patients followed with VHL mutations without an exact location. Patient 26 was a 41Y male. They had a hemangioblastoma tumor 6.7cm3 in size. The mutation p.G114S (c.340G>A) was described in the paper as c.553G>A due to a difference in transcript reference. No family information was provided.
428Y8Y14NNNNNc.340G>AExon 1p.Gly114SerMissense
PatientID: 4
KindredID: 2
Case: F, 14Y0M, Brazilian (Latino/Admixed American)
DiseaseAssertion: VHL
FamilyInfo: None
CasePresentingHPOs: HP:0002666; HP:0030405 (pheochromocytoma, pancreatic endocrine tumor)
CaseHPOFreeText: The patient developed bilateral pheo (as large as L = 6.0cm and R = 5.5cm) at 8Y of age. These recurred after 24months. They later presented with multiple PNET (largest 1.5cm) at 14Y.
CaseNotHPOs: HP:0002668; HP:0005584; HP:0001737; HP:0010797; HP:0009711; HP:0000107 (paraganglioma, renal cell carcinoma, pancreatic cyst, hemangioblastoma, retinal capillary hemangioma, renal cyst)
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.G114S (c.340G>A)
CaseProblemVariantFreeText: N/A
LegacyVariant: N/A
ClinVarID: 583094 https://www.ncbi.nlm.nih.gov/clinvar/variation/583094/
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: missense_variant;transition
CivicName: G114S (c.340G>A)
MultipleGeneVariants: N/A
c.340 G>Aap.G114S
53 patients with a molecularly confirmed VHL mutation (by PCR through EDTA-anticoagulated blood) and a pancreatic neuroendocrine tumor (ICT) were collected from the German NET-Registry and the German VHL-registry. An additional 296 patients were stated in this paper with a VHL associated germline mutation, but without pancreatic neuroendocrine tumors. 2 patients were found to have the above mutation (c.340G>A). 1 was a VHL patient with an ICT (pancreatic neuroendocrine tumor) taken from the VHL-registry. The other patient was stated to be in this study with the given mutation, however no ICT. Other clinical manifestations outside of a pancreatic neuroendocrine tumor are possible, but were not discussed. ACMG evidence codes: 'PP2' because they observe a missense variant in a gene where missense variants are a common mechanism of disease.