Using polymerase chain reaction (PCR)-direct sequencing and universal primer quantitative fluorescent multiplex–PCR, mutations in VHL gene in 19 VHL disease families recruited from the Department of Urology, Peking University First Hospital in the period from 2009 to 2012 were examined. One proband (family 8) was found to carry the mutation c.350G>C in exon 2 of the VHL gene. The proband presented with hemangioblastoma at age 18 and renal cell carcinoma and abnormality of the pancreas at age 24. The patient had negative VHL family history. This patient was previously published in 29330336.

Of 38 PPGL (pheochromocytoma and paraganglioma) cases studied, one was associated with an individual carrying the germline mutation c.350G>C (ENSP00000256474.2 p.Trp117Ser) of the VHL gene. This mutation was identified using germline clinical sequencing on formalin-fixed and paraffin-embedded (FFPE) tissue and confirmed with sanger sequencing. The authors identified the reference sequence used as NM_000551.3. The patient (ID: RNSH08) presented with right adrenal phechromocytoma (31yo). No family history was clear or presented. This patient was previously published in PMID: 25545346.

PatientID: None

KindredID: 8

Case: Unknown, 24Y0M, Chinese

DiseaseAssertion:VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0010797, HP:0005584, HP:0001732 (hemangioblastoma, renal cell carcinoma, abnormality of the pancreas)

CaseHPOFreeText:The patient presented with hemangioblastoma at age 18. At age 24 the patient had renal cell carcinoma and cysts/tumours of the pancreas.

CaseNotHPOs: HP:0009711, HP:0002666(retinal capillary hemangioma, pheochromocytoma)

CaseNotHPOFreeText: No epididymal/ovarian cystadenomas.

CasePreviousTesting: N/A

PreviouslyPublished: 29330336

Variant: p.W117S(c.350G>C)

LegacyVariant:N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.350G%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName:W117S(c.350G>C)

MultipleGeneVariants: N/A

PatientID: 124

KindredID: 44

Case: M, Age 24Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0001732; HP:0005584 (Hemangioblastoma, Pancreatic cysts, Abnormality of the pancreas, Renal cell carcinoma)

CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at 18, renal cell carcinoma and multiple pancreatic cysts/tumors at 24.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in an earlier paper by Wang et al., 2014 (PMID: 24581539) and a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.W117S (c.350G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753671; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.350G%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117S (c.350G>C)

MultipleGeneVariants: N/A