From: Diagnostic yield and clinical utility of a comprehensive gene panel for hereditary tumor syndromes
Patient ID | Sex | Age at last contact | Gene | Mutation (heterozygous) | Predicted gene phenotype | Phenotype of patient |
---|---|---|---|---|---|---|
A) Variants identified in addition to a known germline mutation (group K) | ||||||
Patient with two additional truncating mutations | ||||||
 49197 | m | 1 | NF1 (NM_001042492.2) | c.4107C > A;p.Tyr1369* | Neurofibromatosis type 1 | LFS (TP53 mutation): rhabdomyosarcoma and neuroblastoma (1 y) |
WRN (NM_000553.4) | c.4216C > T;p.Arg1406* | Werner syndrome | ||||
Patients with one additional truncating mutation | ||||||
 41393 | f | 23 | CHEK2 (NM_007194.3) | c.1100delC;p.Thr376Metfs*15 | susceptibility breast cancer | HDGC (CDH1 mutation) |
 35145 | f | 48 | ERCC3 (NM_000122.1) | c.1421dup;p.Asp474Glufs*2 | susceptibility breast cancer (biallelic mutations: Xeroderma pigmentosum (B)) | HNPCC (MSH6 mutation) |
 38982 | m | 30 | FANCD2 (NM_033084.3) | c.990-1G > A | cancer susceptibility? (biallelic mutations: Fanconi anaemia (D2)) | MAP (MUTYH mutations) |
 34429 | m | 59 | PALLD (NM_001166109.1) | c.2269C > T;p.Gln757* | susceptibility pancreatic cancer | HNPCC (MSH2 mutation) |
 30560 | m | 26 | SDHA (NM_004168.3) | c.1432_1432 + 1del;p.? | hereditary paraganglioma-pheochromocytoma syndrome | HNPCC (MSH2 mutation) |
 32679 | f | 32 | XPC (NM_004628.4) | c.622-2A > G | cancer susceptibility? (biallelic mutations: Xeroderma pigmentosum (C)) | MAP (MUTYH mutations) |
Patients with additional potential pathogenic missense / stoploss variants | ||||||
 45126 | f | 53 | BRCA1 (NM_007300.3) | c.5068G > T;p.Ala1690Ser | HBOC | HDGC (CDH1 mutation); gastric and breast cancer, sister breast cancer |
 9691 | f | 59 | MLH1 (NM_000249.3) | c.65G > C;p.Gly22Ala | HNPCC | JPS (SMAD4 mutation) |
 47360 | f | 24 | MSH2 (NM_000251.2) | c.1607A > G;p.Asn536Ser | HNPCC | JPS (BMPR1A mutation) |
 36206 | m | 57 | MSH6 (NM_000179.2) | c.3600A > G;p.Ile1200Met | HNPCC | FAP (APC mutation), two siblings CRC (~  55 y) |
 24320 | f | 68 | MSH6 (NM_000179.2) | c.3664 T > G;p.Phe1222Val | HNPCC | FAP (APC mutation), CRC (68 y), sister CRC (< 64 y) |
 29267 | f | 65 | POLE (NM_006231.3) | c.861 T > A;p.Asp287Glu | PPAP | PJS (STK11 mutation) |
 44792 | m | 39 | RAD51B (NM_133509.3) | c.1155A > T;p.*385Tyrext*64 | breast cancer | HNPCC (MSH2 mutation) |
B) Newly identified variants in patients with previously unknown cause (group U) | ||||||
Patients with likely pathogenic mutations | ||||||
 26356 | f | 9 | PMS2 (NM_000535.5) | c.1A > T;p.Met1? | constitutional mismatch repair deficiency syndrome | multiple tumors: lymphoma (9 y), ALL, CRC (11 y), glioblastoma (15 y); two siblings died because of medulloblastoma / glioblastoma and ALL / astrocytoma |
c.2117delA;p.Lys706Serfs*19 | ||||||
 38569 | m | 58 | POLD1 (NM_002691.3) | c.1379 T > G;p.Lys460Arg | PPAP | adenomatous polyposis (58 y, >  50 colorectal adenomas) + renal cancer (59 y) |
PMS2 (NM_000535.5) | c.2153 T > C;p.Leu718Pro | HNPCC | ||||
 40816 | f | 33 | PTEN (NM_000314.4) | c.83 T > C;p.Ile28Thr | Cowden syndrome | CRC (32 y), duodenal lymphangiectasis, liver hemangioma, polyps or cysts in the ovary and polyps in the cervix uteri; paternal grandmother: cancer of the cervix uteri, CRC, and gastric cancer (> 70 y) |
Patients with two potential pathogenic variants in different genes (at least one truncating mutation) | ||||||
 13225 | m | 67 | BARD1 (NM_000465.3) | c.1690C > T;p.Gln564* | susceptibility breast cancer and neuroblastoma | adenomatous + hyperplastic polyps, brother CRC (40 y) |
XRCC3 (NM_001100119.1) | c.954_957del; p.Ser319Profs*49 | susceptibility several cancer types | ||||
 44298 | m | 73 | FANCF (NM_022725.3) | c.1087C > T;p.Gln363* | cancer susceptibility? (biallelic mutations: Fanconi anaemia (F)) | duodenal polyposis (n = 15, only one was investigated histologically: adenoma), further polyps in small bowel, two colorectal adenomas (73 y) |
BMPR1A (NM_004329.2) | c.712C > G;p.Arg238Gly | juvenile polyposis syndrome | ||||
 38124 | m | 62 | MLH3 (NM_001040108.1) | c.1798C > T;p.Arg600* | HNPCC (?) | member of a family with suspected hyperplastic polyposis syndrome in one cousin, several other family members have some colorectal polyps or colorectal cancer. For patient 38124 only some polyps are reported, no histologic report is available. Five other affected family members have been also investigated with the gene panel, but no one else carries the variants in MLH3 or MUTYH |
MUTYH (NM_001128425.1) | c.667A > G;p.Ile223Val | MUTYH-associated polyposis (biallelic mutations) | ||||
 35847 | f | 64 | POLE (NM_006231.3) | c.6623del;p.Gln2208Argfs*4 | PPAP | adenomatous polyps + familial CRC + other tumors |
APC (NM_000038.5) | c.5009C > T;p.Ala1670Val | FAP | ||||
Patients with truncating mutations | ||||||
 15263 | m | 71 | ATM (NM_000051.3) | c.5932G > T;p.Glu1978* | susceptibility breast cancer (biallelic mutations: Ataxia-Telangiectasia) | hyperplastic polyposis (father of ID 48355) |
 48355 | f | 55 | ATM (NM_000051.3) | c.5932G > T;p.Glu1978* | susceptibility breast cancer (biallelic mutations: Ataxia-Telangiectasia) | hyperplastic polyposis (daughter of ID 15263) |
 45647 | f | 59 | BRIP1 (NM_032043.2) | c.2684_2687delCCAT;p.Ser895* | susceptibility breast and ovarian cancer (biallelic mutations: Fanconi anaemia (J)) | hyperplastic polyposis, father pancreatic cancer |
 46448 | f | 28 | CHEK2 (NM_007194.3) | c.444 + 1G > A | susceptibility breast cancer | medullary thyroid cancer (27 y) |
 44401 | f | 73 | CHEK2 (NM_007194.3) | c.1100delC;p.Thr376Metfs*15 | susceptibility breast cancer | follicular thyroid cancer (63 y), breast cancer (70 y), paraganglioma (72 y), renal angiomyolipoma |
 48835 | m | 32 | CHEK2 (NM_007194.3) | c.1100delC;p.Thr376Metfs*15 | susceptibility breast cancer | papilly thyroid cancer, NHL (both 31 y), in family thyroid, prostatic and breast cancer |
 32119 | f | 64 | CHEK2 (NM_007194.3) | c.1100delC;p.Thr376Metfs*15 | susceptibility breast cancer | thyroid cancer, breast cancer (55 y) |
 22715 | f | 67 | CHEK2 (NM_007194.3) | c.1555C > T;p.Arg519* | susceptibility breast cancer | uterine cancer (32 y), several adenomas, two with high grade dysplasia (62 + 71 y), son with colorectal polyps |
 47863 | f | 61 | EXT1 (NM_000127.2) | c.1483C > T;p.Gln495* | multiple osteochondromas / exostoses | several tumors in family |
 10317 | m | 35 | FANCE (NM_021922.2) | c.248 + 2dupT | biallelic mutations: Fanconi anaemia | sarcoma (35 y); in family: neuroblastoma, testicular cancer, bronchial cancer |
 19347 | f | 61 | FANCL (NM_001114636.1) | c.1111_1114dupATTA; p.Thr372Asnfs*13 | biallelic mutations: Fanconi anaemia | bilateral breast cancer (43 + 53 y), bronchial cancer (61 y); in family: sarcoma, uterine cancer, pancreatic cancer, bronchial cancer |
 47257 | f | 56 | RAD51C (NM_058216.2) | c.706-1G > A | hereditary breast and ovarian cancer | two synchronous CRCs, 10 colorectal adenomas; endometrial cancer in family |
 28219 | m | 48 | SDHA (NM_004168.3) | c.995dup;p.Val333Cysfs*8 | hereditary paraganglioma-pheochromocytoma syndrome | polyposis |
 10083 | m | 33 | XPC (NM_004628.4) | c.780-1G > A | biallelic mutations: Xeroderma pigmentosum (C) | suspected LFS |
Patients with potential pathogenic missense variants | ||||||
 16335 | m | 40 | APC (NM_000038.5) | c.1631 T > C;p.Ile544Thr | FAP | suspected LFS |
 37416 | m | 29 | APC (NM_000038.5) | c.4292 T > A;p.Met1431Lys | FAP | early CRC (before 30y), MSS in tumor tissue |
 37982 | m | 38 | APC (NM_000038.5) | c.281G > A;p.Arg94His | FAP | CRC (before 40y), MSS in tumor tissue |
 44716 | m | 52 | APC (NM_000038.5) | c.7645C > T;p.Arg2549Cys | FAP | Gastrointestinal stromal tumor |
 17052 | f | 46 | BMPR1A (NM_004329.2) | c.1022G > A;p.Gly341Asp | juvenile polyposis syndrome | ovarian cancer (44 y), CRC and breast cancer in family history |
 46581 | f | 33 | BMPR1A (NM_004329.2) | c.1243G > A;p.Glu415Lys | juvenile polyposis syndrome | bladder cancer 32y |
 18225 | f | 12 | CDH1 (NM_004360.3) | c.1298A > G;p.Asp433Gly | HDGC | suspected LFS |
 45312 | f | 33 | MSH6 (NM_000179.2) | c.3724C > T;p.Arg1242Cys | HNPCC | diffuse gastric cancer (33 y), no HNPCC typical findings in tumor tissue, no CDH1 mutation, suspicious family history |
 43219 | f | 65 | POLD1 (NM_002691.3) | c.961G > A;p.Gly321Ser | PPAP | medullary thyroid cancer (64 y), in family: pancreatic and breast cancer |