Table 2 Clinical features and genotype of patients with variants detected in VHL gene (NM_000551)
Case no | Sex | Age at diagnosis in years | Presenting tumor | Other tumors (s)/feature(s) | Variation identified | ACMG classification | Criteria | Family history | Clinical diagnostic criteria met# | Pre-symptomatic testing of family members |
|---|---|---|---|---|---|---|---|---|---|---|
01 | M | 15 | Cerebellar hemangioblastoma | No | c.337C > T p.Arg113Ter | Pathogenic | PVS1, PM2, PP3, PP5 | + | Yes | Father- same variation identified |
02 | M | 46 | Cerebellar hemangioblastoma | No | c.556G > A p.Glu186Lys | Likely pathogenic | PS1, PM1, PM2, PP3 (Reported in clinvar) | − | No | No |
03 | M | 37 | Renal cell carcinoma (bilateral) | No | c.194C > T p.Ser65Leu | Likely pathogenic | PM1, PM2, PP3, PP5 | + | Yes | Son-no variation identified |
04 | M | 13 | Pheochromocytoma (B/L) | No | c.556G > A p.Glu186Lys | Likely pathogenic | PS1, PM1, PM2, PP3 (Reported in clinvar) | − | No | No |
05 | M | 27 | Cerebellar hemangioblastoma | Pheochromocytoma (B/L) | c.500G > A p.Arg167Gly | Likely pathogenic | PM1, PM2, PM5, PP3 | + | Yes | No |
06 | M | 30 | Renalangiomyolipoma, pancreatic and epididymal cyst | – | c.337C > T p.Arg113 Ter | Pathogenic | PVS1, PM2, PP3, PP5 | + | Yes | Brother-same variation identified |
07 | M | 31 | Renal cell carcinoma (B/L) | Pheochromocytoma (B/L) | c.597delG p.Glu199fsTer3## | VUS | PVS1, PM2 | − | Yes | Daughter-no variation identified Son-same variation identified |
08 | F | 27 | Cerebellar hemangioblastoma | No | c.556G > A p.Glu186Lys | Likely pathogenic | PS1, PM1, PM2, PP3 (Reported in clinvar) | − | No | No |
09 | M | 11 | Pheochromocytoma(B/L) | No | c.382C > T p.Leu128Phe | VUS; upgraded to Likely pathogenic | PM1, PM2, PP3, PS4 | − | No | Brother-same variation identified Father-no variation identified |
10 | M | 36 | Cerebellar hemangioblastoma | No | c.233A > G p.Asn78Ser | Likely pathogenic (Pathogenic in Clinvar) | PM1, PM2, PP3, PP5 | − | No | Sister-no variation identified |
11 | F | 14 | Endolymphatic sac papillary tumor | No | c.563 T > C p.Leu188Pro | Likely pathogenic | PM1, PM2, PP3, PP5 | − | No | No |
12 | M | 28 | Pancreatic cyst | No | c.277G > C p.Gly93Arg | Likely pathogenic | PM1, PM2, PM5, PP3 | + | Yes | No |
13 | M | 16 | Cerebellar hemangioblastoma | Pheochromocytoma (B/L) | c.277G > C p.Gly93Arg | Likely pathogenic | PM1, PM2, PM5, PP3 | − | Yes | No |
14 | M | 13 | Pheochromocytoma (B/L) | No | c.500G > A p.Arg167Gln | Likely pathogenic | PM1, PM2, PM5, PP3 | − | No | No |
15 | M | 22 | Pheochromocytoma (right) | No | c.467A > G p.Tyr156Cys | Likely pathogenic | PM1, PM2, PP3, PP5 | − | No | No |
16 | F | 25 | Pheochromocytoma (B/L) | No | c.466 T > C p.Tyr156His | VUS, upgraded to Likely pathogenic | PM1, PM2, PP3, PP4 | − | No | Son and daughter-same variation identified |
17 | F | 27 | Cerebellar hemangioblastoma | No | c.257C > T p.Pro86Leu | Likely pathogenic | PM1, PM2, PP3, PP5 | − | No | No |
18 | M | 16 | Pheochromocytoma (B/L) | No | c.467A > G p.Tyr156Cys | Likely pathogenic | PM1, PM2, PP3, PP5 | − | No | Father-same variation identified Mother and sister-no variation identified |
19 | F | 12 | Pheochromocytoma (B/L) | No | c.482G > A p.Arg161Gln | Likely pathogenic | PM1, PM2, PP3, PP5 | + | Yes | Brother and sister-same variation identified |
20 | F | 12 | Pheochromocytoma (Right) | No | c.239G > A p.Ser80Asn | Likely pathogenic | PM1, PM2, PM5, PP3 | + | Yes | No |
21 | M | 14 | Pheochromocytoma (B/L) | No | c.340G > A p.Gly114Ser | Likely pathogenic | PM1, PM2, PP3, PP5 | − | No | No |
22 | M | 12 | Pheochromocytoma (B/L) | No | c.256C > T p.Pro86Ser | Likely pathogenic | PM1, PM2, PP3, PP5 | − | No | No |
23 | F | 17 | Pheochromocytoma (B/L) | No | c.382C > T p.Leu128Phe | VUS; upgraded to Likely pathogenic | PM1, PM2, PP3, PS4 | − | No | No |
24 | M | 13 | Intramedullary hemangioblastoma | No | c.217insC (c.217dup) p.Gln73Profs Ter 59 | Pathogenic (Reported in HGMD) | PVS1, PS1, PM1, PM2 | − | No | No |
25 | M | 34 | Pheochromocytoma (B/L) | No | c.583C > T p.Gln195 Ter | Pathogenic (Reported in Clinvar) | PVS1, PM2, PP5 | − | No | No |
26 | M | 17 | Pheochromocytoma (B/L) | No | c.499C > T p.Arg167Trp | Pathogenic | PS3, PM1, PM2, PP3, PP5 | − | No | Father, mother and sister-no variation identified |
27 | M | 23 | Pheochromocytoma (B/L) | No | c.499C > T p.Arg167Trp | Pathogenic | PS3, PM1, PM2, PP3, PP5 | − | No | No |
28 | F | 46 | Pheochromocytoma (B/L) | No | c.335A > G p.Asn112Cys | Likely pathogenic | PM1, PM2, PP3, PP5 | − | No | Mother-no variation identified |
29 | M | 15 | Cerebellar hemangioblastoma | Pheochromocytoma (B/L) | c.482G > A p.Arg161Gln | Likely pathogenic | PM1, PM2, PP3, PP5 | − | Yes | No |
30 | M | 10 | Pheochromocytoma (B/L) | No | c.499C > T p.Arg167Trp | Pathogenic | PS3, PM1, PM2, PP3, PP5 | − | No | No |
31 | F | 29 | Cerebellar hemangioblastoma | Pheochromocytoma (B/L) | c.500G > A p.Arg167Gln | Likely pathogenic | PM1, PM2, PM5, PP3 | − | Yes | No |
32 | M | 46 | B/L Renal cell carcinoma | – | Heterozygous deletion of exon 3 ( MLPA) | − | No | No |