Table 1.
Germline variants identified among 95 ovarian cancer patients with next generation sequencing of a 10-gene panel.
| Patient | Gene | HGVS Coding | HGVS Protein | VAF | ClinVar | MetaLR 1 | MetaSVM 1 | C-Score 1 | Varsome | Additional Tests | Personal History (Age 2) | Family History |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OC09 | BRCA1 | c.2037delinsCC | p.(Lys679AsnfsTer4) | 60% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (46) | 4 × OC, 2 × PaC, 1 × GC |
| OC11 | BRIP1 | c.2477A>G | p.(Asn826Ser) | 74% | VUS | D | D | 26.3 | VUS | N/A | OC (39) | 1 × CRC, 1 × L |
| OC12 | BRCA1 | c.211A>G | p.(Arg71Gly) | 81% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (58) | 2 × BC, 1 × PC |
| OC16 | RAD51C | c.709C>T | p.(Arg237Ter) | 81% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (57) | 1 × OC |
| OC17 * | RAD51D | c.748del | p.(His250ThrfsTer2) | 68% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (57) | 2 × OC, 2 × BC, 1 × CRC |
| OC19 | BRCA1 | c.3331_3334del | p.(Gln1111AsnfsTer5) | 81% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (61) | 4 × BC, 1 × OC |
| OC23 | BRCA1 | c.3817C>T | p.(Gln1273Ter) | 92% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (46) | 6 × BC, 1 × CRC |
| OC24 | MSH6 | c.3848_3862del | p.(Ile1283_Tyr1287del) | 45% | N/A | N/A | N/A | N/A | N/A | IHC: loss of expression | OC (51), UC (51) | 2 × BC, 1 × CRC,1 × LC |
| OC29 | BRCA2 | c.5073dup | p.(Trp1692MetfsTer3) | 81% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (48), BC (48) | 3 × BC, 3 × PC, 3 × CRC |
| OC30 * | RAD51D | c.748del | p.(His250ThrfsTer2) | 81% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (73) | 2 × OC, 2 × BC, 1 × CRC |
| OC31 | RAD51C | c.709C>T | p.(Arg237Ter) | 77% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (62) | 1 × BC |
| OC36 | BRCA2 | c.8036A>G | p.(Asp2679Gly) | 36% | CIP | D | D | 31 | LP | N/A | OC (59) | 1 × CRC, 1 × |
| OC37 | MSH6 | c.1729C>T | p.(Arg577Cys) | 43% | VUS | D | D | 34 | VUS | IHC: normal; MSI: normal | OC (68) | 1 × LC |
| OC39 | BRCA1 | c.3331_3334del | p.(Gln1111AsnfsTer5) | 69% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (63) | 2 × BC, 1 × CRC |
| OC40 | BRCA1 | c.3331_3334del | p.(Gln1111AsnfsTer5) | 58% | Pathogenic | N/A | N/A | N/A | N/A | N/A | BC (49), OC (50) | --------- |
| OC50 | BRCA2 | c.9364G>C | p.(Ala3122Pro) | 88% | VUS | D | D | 31 | LP | N/A | OC (62) | 1 × CRC, 1 × BC, 1 × PC |
| OC52 | BRCA1 | c.2037_2038insC | p.(Lys680GlnfsTer3) | 54% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (52) | 2 × BC, 1 × PC |
| OC54 | RAD51D | c.748del | p.(His250ThrfsTer2) | 93% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (48) | 2 × BC, 1 × PC, 3 × CRC |
| OC55 * | RAD51D | c.748del | p.(His250ThrfsTer2) | 56% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (54) | 2 × OC, 2 × BC, 1 × CRC |
| OC60 | BRCA2 | c.7975A>G | p.(Arg2659Gly) | 62% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (56) | 3 × BC, 1 × PaC, 1 × CRC |
| OC72 | BRCA2 | c.5073dup | p.(Trp1692MetfsTer3) | 56% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (60) | 1 × PaC, 1 × PC |
| OC73 | BRCA2 | c.5073dup | p.(Trp1692MetfsTer3) | 86% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (44) | 2 × BC, 1 × CRC |
| OC79 | MSH6 | c.3182T>C | p.(Leu1061Pro) | 48% | VUS | D | D | 24.8 | VUS | IHC: loss of expression | OC (49) | 1 × CRC |
| OC88 | BRCA2 | c.2T>G | p.Met1? | 93% | Pathogenic | N/A | N/A | N/A | N/A | N/A | BC (59), OC (69) | 1 × BC, 1 × PC |
| OC91 | TP53 | c.845G>A | p.(Arg282Gln) | 47% | VUS | D | D | 35 | LP | N/A | OC (58), TC (60), PaC (60) | 1 × GC, 1 × CRC, BC |
| OC93 | BRCA2 | c.8488-1G>A | --------- | 57% | Pathogenic | N/A | N/A | N/A | N/A | N/A | OC (65) | 1 × BC, 1 × PaC |
BC: Breast cancer; CIP: conflicting interpretations of pathogenicity; CRC: Colorectal cancer; GC: gastric cancer; IHC: Immunohistochemistry; L: Lymphoma; LC: Lung cancer; LP: Likely pathogenic; MSI: Microsatellite instability; N/A: not available; OC: ovarian cancer; PaC: Pancreatic cancer; PC: Prostate cancer; UC: uterine cancer; VAF: variant allele frequency; VUS: variant of unknown significance. * OC17, OC30, and OC55 belong to the same family. 1 Missense variants were retained if they were predicted to be damaging (D) by MetaLR, MetaSVM, and CADD-score (>15). 2 Age at diagnosis.