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Table 4 Most interesting variants. All variants were heterozygous. Clear pathogenic mutations are shown in bold

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
 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
  1. ALL = Acute Lymphoblastic Leukemia, CRC = Colorectal Cancer, FAP = Familial adenomatous polyposis, HBOC = hereditary breast and ovarian cancer, HDGC = hereditary diffuse gastric cancer, HNPCC = hereditary nonpolyposis colorectal cancer, JPS = Juvenile Polyposis Syndrome, LFS = Li-Fraumeni Syndrome, MAP = MUTYH-associated Polyposis, MSS = microsatellite stability, PJS = Peutz-Jeghers Syndrome, PPAP = Polymerase-Proofreading Associated Polyposis, y = years of age, age at first diagnosis, * = termination codon