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| Paraganglioma_phaeochromocytoma v0.30 | VHL | Zornitza Stark Marked gene: VHL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paraganglioma_phaeochromocytoma v0.30 | VHL | Zornitza Stark Gene: vhl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paraganglioma_phaeochromocytoma v0.29 | EPAS1 |
Chirag Patel gene: EPAS1 was added gene: EPAS1 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review,Literature Mode of inheritance for gene: EPAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EPAS1 were set to PMID: 22931260, 23418310, 33300499 Phenotypes for gene: EPAS1 were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Pheochromocytoma/paraganglioma, susceptibility to, no MIM#; Erythrocytosis, familial, 4, MIM#611783 Review for gene: EPAS1 was set to RED Added comment: PMID: 22931260 2 somatic gain-of-function variants in EPAS1 gene encoding hypoxia-inducible factor 2α (HIF2A) in two patients (1 x paraganglioma, 1 x paraganglioma + somatostatinoma). Both patients had polycythemia (congenital erythrocytosis). The two variants were associated with increased HIF-2α activity and increased protein half-life. PMID: 23418310 7 patients with somatic variants in EPAS1 gene (4 x multiple PGLs, 3 x single sporadic PCC/PGL). Gene expression analysis of EPAS1-mutated tumours revealed similar mRNA EPAS1 levels to those found in SDH-gene- and VHL-mutated cases and a significant up-regulation of two hypoxia-induced genes (PCSK6 and GNA14). Multiplex-PCR screening for small rearrangements detected a specific EPAS1 gain in another EPAS1-mutated tumour and in 3 non-EPAS1-mutated cases. PMID: 33300499 6 germline missense variants in EPAS1 gene in patients with PPGL (Arg247Ser, Phe374Tyr, His194Arg, Pro785Thr, Ile789Val, Thr766Pro). In transient transfection studies, EPAS1/HIF-2α Arg247Ser, Phe374Tyr and Pro785Thr were all stable in normoxia. In co-immunoprecipitation assays, only the Arg247Ser variant showed diminished interaction with pVHL. A direct interaction between HIF-2α Arg247 and pVHL was confirmed in structural models. Transactivation was assessed by means of a HRE-containing reporter gene in transiently transfected cells, and significantly higher reporter activity was only observed with EPAS1/HIF-2α Phe374Tyr and Pro785Thr. In conclusion, three germline EPAS1 variants (c.739C>A (p.Arg247Ser), c.1121T>A (p.Phe374Tyr) and c.2353C>A (p.Pro785Thr)) all have some functional features in common with somatic activating mutations. Their findings suggest that these three germline variants are hypermorphic alleles that may act as modifiers to the expression of PPGLs. Sources: Expert list, Expert Review, Literature |
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| Paraganglioma_phaeochromocytoma v0.9 | VHL | Chirag Patel Classified gene: VHL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paraganglioma_phaeochromocytoma v0.9 | VHL | Chirag Patel Gene: vhl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paraganglioma_phaeochromocytoma v0.8 | VHL |
Chirag Patel gene: VHL was added gene: VHL was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: VHL were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Von Hippel-Lindau disease, MONDO:0008667; von Hippel-Lindau syndrome, MIM#193300; Pheochromocytoma, susceptibility to, MIM#171300 Review for gene: VHL was set to GREEN Added comment: ClinGen definitive. Paragangliomas and phaeochromocytomas reported in condition. Sources: Expert list, Expert Review |
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