Table 2.
Patients with a genetic variant in the E1' cryptic exon of VHL gene
| Patient number | Phenotype (age at first diagnosis) |
Follow-up duration (years) | Germline genetic variant | dbSNP ID | Allele frequency* (%) |
LOH | Somatic VHL mutation | CAIX IHC |
PNMT and VHL (E1-E2) expression | VHL (E1-E1’ expression | Classification of VUS |
| #1 | Carotid body PGL (47) | 5 | c.340+563C>T | NA | No† | ND | Neg | ND | ND | Benign | |
| #2 | Carotid body PGL (34) | 1 | c.340+578C>T | rs139622356 | 0.05 | NA | NA | NA | NA | NA | VUS |
| #3 | PCC (38) |
7 | c.340+578C>T | rs139622356 | 0.05 | No | No | Neg | Normal | Increase | VUS |
| #4 | Carotid body PGL (74) | 1 | c.340+578C>T | rs139622356 | 0.05 | NA | NA | NA | NA | NA | VUS |
| #5 | Carotid body PGL (56) | 1 | c.340+578C>T | rs139622356 | 0.05 | NA | NA | NA | NA | NA | VUS |
| #6 | PGL+ccRCC (81–82) |
2 | c.340+578C>T | rs139622356 | 0.05 | NA | NA | NA | NA | NA | VUS |
| #7 | bilccRCC (49–51) |
NA | c.340+578C>T | rs139622356 | 0.05 | NA | NA | NA | NA | NA | VUS |
| #8 | ccRCC (39) |
NA | c.340+578C>T | rs139622356 | 0.05 | NA | NA | NA | NA | NA | VUS |
| #9 | Multiple retinal HMB (36) | 32 | c.340+617C>G‡ | NA | NA | NA | NA | NA | NA | Pathogenic | |
| #10 | PCC (11) |
15 | c.340+682T>C | NA | No | c.482G>A p.R161Q | Pos | Decrease | Increase | Pathogenic | |
| #11 | Multiple HN PGL (12) | 1 | 340+725A>T | NA | NA | NA | NA | NA | NA | VUS | |
| #12 | PCC (34) |
10 | c.340+866C>A | rs536631685 | 0.02 | NA | NA | NA | NA | NA | VUS |
*Frequency in gnomAD or 1000 Genomes,.
†loss of the mutated allele.
‡Mutation described in Lenglet et al.8
bilccRCC, bilateral clear cell renal cell carcinoma; ccRCC, clear cell renal cell carcinoma; HMB, haemangioblastoma; HN, head and neck; LOH, loss of heterozygosity; NA, none available; ND, not done; Neg, negative immunochemistry; PCC, pheochromocytoma; PGL, paraganglioma; Pos, positive immunochemistry; VHL, von Hippel-Lindau; VUS, variant of uncertain significance.