Table 2.
(Likely) pathogenic variants (ACMG classes 4/ 5) identified in tumor samples.
| Diagnosis | AD/Gender | Gene | Nucleotide Change | Amino Acid Change | VAF (Tumor) | LOH | Somatic Status | Germline Testing * | S:F Ratio | |
|---|---|---|---|---|---|---|---|---|---|---|
| ID80 | PHEO | 65/m | ATRX | c.1441G > T | p.(Glu481*) | 5.4% | no | likely somatic | no | 46.2 |
| ID82 | PHEO | 31/f | FH | c.700A > G | p.(Thr234Ala) | 82.0% | yes | germline | yes (targeted) | 0.4 |
| ID41 | PHEO | 37/m | FH | c.816_836del | p.(Ala273_Val279del) | 92.3% | yes | germline | yes (targeted) | 0.3 |
| ID68 | PHEO | 66/f | HRAS | c.182A > G | p.(Gln61Arg) | 56.8% | no | somatic | yes | 66.3 |
| ID1 | PHEO | 52/f | HRAS | c.182A > G | p.(Gln61Arg) | 72.0% | somatic | yes | 17.7 | |
| ID60 | PHEO | 27/f | HRAS | c.37G > C | p.Gly13Arg | 26.0% | no | somatic | no | 12.8 |
| ID75 | HNP | 53/f | IDH2 | c.514A > G | p.Arg172Gly | 24.5% | no | somatic | yes (targeted) | 5.3 |
| ID73 | PHEO | 56/f | NF1 | c.1540C > T | p.(Gln514*) | 62.1% | unknown | no | 16.6 | |
| ID79 | PHEO | 58/f | NF1 | c.7798_7799insA | p.(Ser2601fs) | 83.2% | yes | unknown | no | 47.5 |
| ID91 | PHEO | 50/m | NF1 | c.205-1G > T | p.? | 39.9% | no | unknown | no | unknown |
| ID92 | PHEO | 73/f |
NF1
NF1 |
c.1318C > T c.7549C > T |
p.(Arg440*) p.(Arg2517*) |
15.9% 33.2% |
no no |
likely somatic unknown |
no | unknown unknown |
| ID51 | PGL | 56/m | SDHB | c.183T > G | p.(Tyr61*) | 80.0% | yes | somatic | yes (targeted) | 5178.2 |
| ID42 | PGL | 51/m | SDHB | c.287-3C > G | p.? | 85.4% | yes | germline | yes | 1472.7 |
| ID71 | HNP | 49/m | SDHB | c.724C > T | p.(Arg242Cys) | 16.4% | no | likely somatic | no | 24.7 |
| ID43 | PHEO | 50/m |
SDHC
ATRX |
c.379C > T c.2817del |
p.(His127Tyr) p.(Ala940fs) |
46.6% 65.8% |
no | germline likely somatic |
yes | 795.5 |
| ID69 | HNP | 27/f | SDHD | c.3G > T | p.(Met1Ile) | 18.2% | no | somatic | yes | 405.9 |
| ID24 | PGL | 21/m | SDHD | c.337_340del | p.(Asp113fs) | 41.5% | somatic | yes | 1756.8 | |
| ID72 | PHEO | 66/f |
TP53
ATRX |
c.817C > T c.4744_4745insA |
p.(Arg273Cys) p.(Thr1582fs) |
74.1% 61.2% |
somatic unknown |
yes | 5.7 | |
| ID67 | PGL | 31/f | VHL | c.193T > G | p.(Ser65Ala) | 8.5% | no | somatic | yes | 24.1 |
| ID66 | PHEO | 13/m | VHL | c.193T > G | p.(Ser65Ala) | 17.4% | no | somatic | yes | 21.4 |
| ID78 | PHEO | 47/f | VHL | c.500G > A | p.(Arg167Gln) | 49.6% | no | unknown | no | 17.4 |
* Information about germline status was either available from routine germline testing in the patients included from our clinical cohort (indicated with “Germline testing yes”) or due to targeted Sanger sequencing of blood samples (“yes (targeted)”). ACMG: American College of Medical Genetics, AD: age at diagnosis, LOH: loss of heterozygosity PHEO: pheochromocytoma, PGL: paraganglioma, HNP: head and neck paraganglioma, S:F ratio: succinate to fumarate ratio, VAF: variant allele frequency.