Table 2

Patients with a genetic variant in the E1' cryptic exon of VHL gene

Patient numberPhenotype
(age at first diagnosis)
Follow-up duration (years)Germline genetic variantdbSNP IDAllele frequency*
(%)
LOHSomatic VHL mutationCAIX
IHC
PNMT and VHL (E1-E2) expressionVHL (E1-E1’ expressionClassification of VUS
#1Carotid body PGL (47)5c.340+563C>TNANo†NDNegNDNDBenign
#2Carotid body PGL (34)1c.340+578C>Trs1396223560.05NANANANANAVUS
#3PCC
(38)
7c.340+578C>Trs1396223560.05NoNoNegNormalIncreaseVUS
#4Carotid body PGL (74)1c.340+578C>Trs1396223560.05NANANANANAVUS
#5Carotid body PGL (56)1c.340+578C>Trs1396223560.05NANANANANAVUS
#6PGL+ccRCC
(81–82)
2c.340+578C>Trs1396223560.05NANANANANAVUS
#7bilccRCC
(49–51)
NAc.340+578C>Trs1396223560.05NANANANANAVUS
#8ccRCC
(39)
NAc.340+578C>Trs1396223560.05NANANANANAVUS
#9Multiple retinal HMB (36)32c.340+617C>G‡NANANANANANAPathogenic
#10PCC
(11)
15c.340+682T>CNANoc.482G>A p.R161QPosDecreaseIncreasePathogenic
#11Multiple HN PGL (12)1340+725A>TNANANANANANAVUS
#12PCC
(34)
10c.340+866C>Ars5366316850.02NANANANANAVUS
  • *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.