A study investigated paraganglioma/pheochromocytoma tumors in a retrospective cohort and a prospective cohort. Some of these tumors were found with germline VHL mutations. Tumor ID 11 (paraganglioma) and 12 (pheochromocytoma) belonged to one 26Y old patient with a germline p.Pro154Ser VHL mutation. Patient data is extracted from two rows assumed to be referring to the same patient (i.e. tumor samples 11 and 12 in Supplementary Table 1a). Other phenotypic and demographic information was not available.

314 Chinese patients with Pheochromocytoma/paraganglioma (PPGL) from Peking Union Medical College Hospital, China, were included in this study for germline profiling. The majority of patients underwent surgery and were histopathologically diagnosed with PPGL. For patients who had an unresectable or metastatic tumor, PPGL diagnosis was determined based on clinical features (headache, palpitations, sweating, etc). Genomic DNA was extracted from peripheral blood of all 314 PPGL patients, and detect potential variants in 12 known genes associated with hereditary PPGL (SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, RET, NF1, MAX, TMEM127, and KIF1B) using next-generation and Sanger sequencing. Germline variants were detected in 29% of the 314 PPGL patients. Patient #89 is a female PPGL patient who was diagnosed with retroperitoneal paraganglioma at age 39. She was also 39 when metastasis was detected. Germline genetic testing revealed a missense p.P154S(c.460C>T) variant in exon 2 of the VHL gene. Patient 89 does not have family history of PPGL.

A 65Y male patient of Japanese ethnicity presented with hypertension, bilateral adrenal pheochromocytoma, and hepatic hemangioma. A mutation NM_000551.3:c.460C>T (p.Pro154Ser) was found in the VHL gene. Genetic sequencing occurred through PCR testing and RFLP analysis. Please note that the paper does not state a reference sequence, and instead refers to the mutation as the first base of codon 154. His 35Y son had the same mutation and presented with right adrenal pheochromocytoma. His wife, another son, and daughter were healthy and had normal genetic testing results. ACMG: PP2, PP1, PP4

PatientID: 89

KindredID: 89

Case: F, 39Y0M, Chinese (East Asian)

DiseaseAssertion: Paraganglioma

FamilyInfo: No family history.

CasePresentingHPOs: Paraganglioma (HP:0002668)

CaseHPOFreeText: retroperitoneal paraganglioma 6.8cm in size; metastatic. Age of diagnosis at 39Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154S (c.460C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 486714 https://www.ncbi.nlm.nih.gov/clinvar/variation/486714

CAID: N/A

gnomAD: N/A

VariantEvidence: Described as a pathogenic variant, according to the ACMG guidelines at the time of publication.

MutationType: missense_variant;transition

CivicName: P154S (c.460C>T)

MultipleGeneVariants: N/A