Full Comprehensive Cancer Panel

  • Panel Description
  • Test Description
  • CPT Codes
  • Resources
  • Gene Descriptions

Panel Description

Hereditary Cancer and Cancer SyndromesThe Full Comprehensive Cancer Panel examines 127 genes associated with hereditary cancer. This panel includes both well-established genes that increase a person’s risk for cancer, but also includes candidate genes that may have only been recently discovered or for which additional research is needed. This panel maximizes the chances of identifying a pathogenic cancer susceptibility variant, while providing a comprehensive review of candidate genes to give you information you can use now and potentially in the future.

Adults with a personal or family history suggestive of a hereditary cancer syndrome. Red flags for a hereditary cancer susceptibility could include onset of cancer prior to the age of 50 years, more than one primary cancer in a single person, and multiple affected people within a family. After consideration of a patient’s clinical and family history, this testing may be appropriate for some pediatric patients. (If there are specific genes that you do NOT want included, please indicate this on the test requisition form.) This test is designed to detect individuals with a germline pathogenic variant, and is not validated to detect mosaicism below the level of 20%. It should not be ordered on tumor tissue.

Patients identified with hereditary cancer susceptibility can benefit from increased surveillance and preventative steps to better manage their risk for cancer. Knowing the specific gene involved can guide medical management and avoid unnecessary follow up. Information obtained from candidate gene testing may be helpful in guiding clinical management in the future. Also, your patient’s family members can be tested to help define their risk. If a pathogenic variant is identified in your patient, close relatives (children, siblings, parents) could have as high as a 50% risk to also be at increased risk. In some cases, screening should begin in childhood.

Test Description

  • Sequencing
  • Del/Dup
  • Rush / STAT
  • Exclude VUS
2 - 3 weeks
Call for details
AIP, ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, BUB1B, CASR, CDC73, CDH1, CDK4, CDKN1B, CDKN1C, CDKN2A, CEBPA, CHEK2, CTC1, CTNNA1, CYLD, DDB2, DICER1, DIS3L2, DKC1, EGLN1, EPCAM, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, EXT1, EXT2, EZH2, FAN1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FH, FLCN, GALNT12, GATA2, GPC3, GREM1, HOXB13, HRAS, KIF1B, KIT, LZTR1, MAX, MC1R, MEN1, MET, MITF, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, NHP2, NOP10, NTHL1, PALB2, PDGFRA, PHOX2B, PMS2, POLD1, POLE, POLH, POT1, PRKAR1A, PRSS1, PTCH1, PTCH2, PTEN, RAD50, RAD51C, RAD51D, RB1, RECQL4, RET, RUNX1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SLC45A2, SLX4, SMAD4, SMARCA4, SMARCB1, SMARCE1, STK11, SUFU, TERC, TERT, TINF2, TMEM127, TP53, TSC1, TSC2, TYR, VHL, WRAP53, WRN, WT1, XPA, XPC, XRCC2 ( 127 genes )
99% at 50x
Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)
Test results and variant interpretation are based on the proper identification of the submitted specimen and use of correct human reference sequences at the queried loci. In very rare instances, errors may result due to mix-up or co-mingling of specimens. Positive results do not imply that there are no other contributions, genetic or otherwise, to the patient's phenotype, and negative results do not rule out a genetic cause for the indication for testing. Official gene names change over time. Fulgent uses the most up to date gene names based on HUGO Gene Nomenclature Committee (https://www.genenames.org) recommendations. If the gene name on report does not match that of ordered gene, please contact the laboratory and details can be provided. Result interpretation is based on the collected information and Alamut annotation available at the time of reporting. This assay is not designed or validated for the detection of mosaicism. DNA alterations in regulatory regions or deep intronic regions (greater than 20bp from an exon) will not be detected by this test. There are technical limitations on the ability of DNA sequencing to detect small insertions and deletions. Our laboratory uses a sensitive detection algorithm, however these types of alterations are not detected as reliably as single nucleotide variants. Rarely, due to systematic chemical, computational, or human error, DNA variants may be missed. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the confounding contribution of pseudogene sequences or other highly-homologous sequences, sometimes these may still interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Deletion/duplication analysis can identify alterations in genomic regions and is evaluated at a single exon resolution level in relevant genes associated with the patient's clinical presentation. For custom added genes and applicable genes that may be of interest, deletion/duplication analysis is evaluated at a resolution of two or more contiguous exons. When novel DNA duplications are identified, it is not possible to discern the genomic location or orientation of the duplicated segment, hence the effect of the duplication cannot be predicted. Where deletions are detected, it is not always possible to determine whether the predicted product will remain in-frame or not. Unless otherwise indicated, in regions that have been sequenced by Sanger, deletion/duplication analysis has not been performed. Patients with Bone Marrow Transplants: DNA extracted from cultured fibroblasts should be submitted instead of blood/saliva/buccal samples from individuals who have undergone allogeneic bone marrow transplant and from patients with hematologic malignancy.

Gene Notes
GALNT12 Due to high GC content, copy-number variants located in exon 1 of the GALNT12 gene (NM_024642.4) cannot be reliably detected and will not be reported.
MSH2 Inversion of MSH2 exons 1-7 ("Boland" inversion) is assessed for Lynch Syndrome, Colorectal, Endometrial, and Prostate Cancer Panel testing (for both Focus and Comprehensive Panels) as well as Comprehensive Gastric Cancer Panel testing. Unless otherwise specified, this testing is not performed for other cancer panels, but is available upon request.
CPT Code 81455

NOTE:  The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.
WHY ORDER THIS TEST?

Resources

DescriptionDownload
Hereditary Brain Cancer Information for Patients
Hereditary Endometrial Cancer Information for Patients
Fanconi Anemia Genetic Testing Information for Patients
Hereditary Hematologic Malignancy Genetic Testing Information for Patients
Hereditary Breast Cancer Information for Patients
Hereditary Colorectal Cancer Information for Patients
Hereditary Gastric Cancer Information for Patients
Hereditary Melanoma Information for Patients
Hereditary Ovarian Cancer Information for Patients
Hereditary Pancreatic Cancer Information for Patients
Hereditary Paraganglioma-Pheochromocytoma Information for Patients
Hereditary Prostate Cancer Information for Patients
Hereditary Sarcoma Information for Patients
Hereditary Thyroid Cancer Information for Patients
Renal-Urinary Tract Cancer Genetic Testing Information for Patients

Gene Descriptions

Gene Reason Reference
ALK Autosomal dominant pathogenic variants in the ALK gene are associated with familial neuroblastoma, and confer a small increased risk (low penetrance) for this type of cancer. PubMed: 25124476, 28055978
APC Heterozygous pathogenic variants in APC are associated with both classic and attenuated familial adenomatous polyposis (FAP), Gardner syndrome, Turcot syndrome, and Hereditary Desmoid disease. PubMed: 20301519; OMIM: 175100
ATM Heterozygous pathogenic variants in ATM are associated with an increased risk for breast and pancreatic cancer. Additionally, biallelic pathogenic variants in ATM have been associated with ataxia-telangiectasia, which is associated with a higher risk for lymphoma and leukemia. PubMed: 15928302, 22585167, 20301790, 28418444; OMIM: 607585
ATR Autosomal dominant pathogenic variants in ATR are associated with familial cutaneous telangiectasia and cancer syndrome (FCTCS), which confers an increased risk for oropharyngeal cancer, and possibly others. PubMed: 22341969; OMIM: 601215
BARD1 Heterozygous pathogenic variants in the BARD1 gene raise an individual’s risk of developing breast cancer in their lifetime. PubMed:23586058, 28418444; OMIM: 114480
BLM Biallelic pathogenic variants in the BLM gene cause Bloom's syndrome. Individuals with Bloom's syndrome are at a greatly increased risk for many types of cancer, often occurring at younger than typical ages. Patients with Bloom's syndrome are hypersensitive to some forms of cancer treatment. Additionally, carriers of heterozygous pathogenic BLM variants may be at a small increased risk for breast cancer, as well as others (low/moderate penetrance). However, additional studies are needed to confirm an association. PubMed: 20301572, 19432957, 23404160, 24733792, 26358404; OMIM: 210900
BMPR1A Heterozygous pathogenic variants in BMPR1A are associated with Juvenile Polyposis Syndrome (JPS). PubMed: 17303595, 20301642, 9869523; OMIM: 174900
BRCA1 Autosomal dominant pathogenic variants in the BRCA1 gene are the most common cause of hereditary breast and ovarian cancer syndrome (HBOC). PubMed: 9497246, 12677558, 17416853, 20301425, 22846731
BRCA2 Autosomal dominant mutations in the BRCA2 gene are implicated in the hereditary breast and ovarian cancer syndrome (HBOC). Additionally, biallelic mutations in BRCA2 gene are associated with autosomal recessive Fanconi anemia Type D1 . PubMed: 12065746, 12677558, 9497246, 17416853, 18042939, 20301425, 22846731, 22187320
BUB1B Biallelic pathogenic variants in BUB1B are associated with Mosaic variegated aneuploidy syndrome (MVA), which is associated with a high risk for Wilms tumor and other malignancies. PubMed: 20301772,15475955; OMIM: 602860
CASR There is some evidence that pathogenic variants in CASR may also be associated with chronic pancreatitis, which is a risk factor for pancreatic cancer. Additional research is needed to confirm this association, and any increased risk for cancer. PubMed: 18938753, 25400986; OMIM: 601199
RUNX1 Heterozygous pathogenic variants in the RUNX1 gene are associated with familial plately disorder and an increased risk for myeloid malignancies. PubMed: 28179279, 18173751, 11830488
CDH1 Pathogenic heterozygous variants in the CDH1 (E-cadherin) gene are associated with an increased risk for gastric and lobular breast cancer. PubMed: 11729114, 20301318; OMIM: 192090
CDK4 Heterozygous pathogenic CDK4 variants are associated with an increased risk for melanoma and possibly for pancreatic cancer, as well. PubMed: 28283772, 26337759, 17047042
CDKN1B Pathogenic heterozygous variants in CDKN1B are associated with Multiple Endocrine Neoplasia, Type IV (MEN 4). PubMed: 20301710, 23652671, 26257968; OMIM: 610755
CDKN1C Autosomal dominant, maternally inherited, pathogenic variants in the CDKN1C gene are one cause of Beckwith-Wiedemann syndrome, which is associated with an increased risk for embryonal tumors, including Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma, as well as other clinical conditions. PubMed: 20301568; OMIM: 600856
CDKN2A Heterozygous pathogenic CDKN2A variants are associated with an increased risk for hereditary melanoma and familial atypical multiple mole melanoma-pancreatic carcinoma (FAMMPC) syndrome. PubMed: 28283772, 26337759, 21249757, 19260062; OMIM: 600160
CEBPA Heterozygous pathogenic variants in the CEBPA gene are associated with an increased risk for myeloid malignancies. PubMed: 18173751, 10508512
CYLD Autosomal dominant pathogenic variants in the CYLD gene are associated wtih Brooke-Spiegler syndrome, which increases the risk for the development of different types of skin tumors, usually on the head and neck. PubMed: 28110467; OMIM: 605018
DDB2 Biallelic pathogenic variants in DDB2 account for approximately 3% of cases of xeroderma pigmentosum, which increases the risk for several types of skin cancer and other clinical conditions. PubMed: 20301571; OMIM: 278740, 600811
DKC1 X-linked recessive pathogenic variants in DKC1 cause approximately 20-25% of cases of dyskeratosis congenita, which increases the risk for bone marrow failure and other malignancies. PubMed: 20301779; OMIM: 300126
ERCC1 Biallelic pathogenic variants in ERCC1 are associated with xeroderma pigmentosum in rare cases, which increases the risk for skin cancer, as well as other conditions. The evidence that heterozygous germline pathogenic variants in ERCC1 are associated with an increased risk for cancer has been contradictory. Additional research is needed. PubMed: 20301571, 23909490, 25867436, 24841208, 25051148; OMIM: 126380
ERCC2 Biallelic pathogenic variants in the ERCC2 gene have been associated with different phenotypes, including xeroderma pigmentosum complementation group D, as well as other clinical conditions. Individuals with xeroderma pigmentosum have an increased risk to develop skin cancer. To date, heterozygous carriers of alterations in the ERCC2 gene have not been shown to have a significant alteration in cancer risk. PubMed: 20301571, 1729695, 15615908, 27504877; OMIM: 126340
ERCC3 Biallelic pathogenic variants in ERCC3 are a rare cause of xeroderma pigmentosum, which increases an individual's risk for skin cancer, as well as other clinical conditions. PubMed: 20301571; OMIM: 133510
ERCC4 Biallelic pathogenic variants in ERCC4 have been associated with Fanconi anemia complementation group Q, xeroderma pigmentosa, cockayne syndrome and XFE progeroid syndrome. At this time, carriers of one pathogenic ERCC4 variant have not been shown to have an increased risk for cancer, although additional research is needed for confirmation. PubMed: 20301575, 23623386, 24027083
ERCC5 Biallelic pathogenic variants in ERCC5 are associated with xeroderma pigmentosum, complementation group G, which increases an individual's risk for skin cancer and other clinical conditions. PubMed: 20301575
EXT1 Autosomal dominant pathogenic variants in EXT1 are associated with Hereditary Multiple Osteochondromas (HMO). Individuals with HMO generally develop multiple osteochondromas which can degrade into a chondrosarcoma, although the lifetime risk for this to occur is approximately 2-5%. PubMed: 20301413 ; OMIM: 608177
EXT2 Autosomal dominant pathogenic variants in EXT2 are associated with Hereditary Multiple Osteochondromas (HMO). Individuals with HMO generally develop multiple osteochondromas which can degrade into a chondrosarcoma, although the lifetime risk for this to occur is approximately 2-5%. PubMed: 20301413; OMIM: 608210
EZH2 Autosomal dominant pathogenic variants in EZH2 are associated with EZH2-related overgrowth syndromes and an increased risk for neuroblastoma. Additional research is needed to quantify the risk. PubMed: 23865096; OMIM: 601573
FANCA Biallelic pathogenic variants in FANCA are the most common cause of Fanconi Anemia, accounting for approximately 60-70% of cases. PubMed: 20301575; OMIM: 607139, 227650
FANCC Biallelic pathogenic variants in FANCC are responsible for approximately 14% of Fanconi Anemia cases. Studies examining cancer risk for heterozygous carriers of pathogenic FANCC variants are contradictory, and additional research is needed. PubMed: 20301575, 12750283, 14726700, 26778106; OMIM: 613899, 227645
FANCD2 Biallelic pathogenic variants in FANCD2 cause Fanconi Anemia, complementation group D2. PubMed: 20301575; OMIM: 613984, 227646
FANCE Biallelic pathogenic variants in FANCE cause Fanconi Anemia, complementation group E. PubMed: 20301575; OMIM: 613976, 60091
FANCB Hemizygous pathogenic FANCB variants cause an X-linked recessive form of Fanconi Anemia. PubMed: 20301575, 12750283; OMIM:
FANCF Biallelic pathogenic variants in FANCF cause Fanconi Anemia, complementation group F. PubMed: 20301575; OMIM: 613897, 603467
FANCG Biallelic pathogenic variants in FANCG cause Fanconi Anemia, complementation group G. Early studies examining pancreatic risk for heterozygous carriers of pathogenic FANCG variants suggest a possible increased risk. However, additional studies are needed to confirm this association. PubMed: 20301575, 12750283, 14726700; OMIM: 602956, 614082
FH Heterozygous germline pathogenic variants in FH are associated with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). Biallelic pathogenic variants in the FH gene cause fumarate hydratase deficiency. PubMed: 20301430, 20301679; OMIM: 136850
GATA2 Autosomal dominant pathogenic variants in GATA2 are associated with GATA2 deficiency and Emberger syndromes, both of which increase an individual's risk for myelodysplasia and acute myeloid leukemia. PubMed: 24227816, 28179280; OMIM 137295, 614038
GPC3 X-linked loss of function pathogenic variants in the GPC3 gene have been associated with type 1 Simpson-Golabi-Behmel syndrome which is an overgrowth syndrome that may include multiple congenital anomalies including intellectual disability, distinctive craniofacial features, organomegaly, and an increased risk of embryonal tumors, including Wilms tumor, hepaoblastoma and hepatocellular carcinoma, among others. PubMed: 25238977, 24459012; OMIM: 300037
MSH6 Autosomal dominant pathogenic variants in MSH6 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome. Biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065; OMIM: 120436
HRAS Heterozygous pathogenic variants in HRAS cause Costello syndrome. Individuals with Costello syndrome have a 15% lifetime risk for developing a malignant tumor, which can include rhabdomyosarcoma, neuroblastoma, and carcinoma of the bladder. PubMed: 20301680; OMIM: 190020
KIT Heterozygous germline mutations in the KIT gene have been associated with different phenotypic expressions, including familial gastrointestinal stromal tumor syndrome, mast cell disease (mastocytosis) and piebaldism. As association between germline pathogenic KIT variants with core binding factor acute myeloid leukemia and acute lymphoblastic leukemia has been suggested, but additional research is needed. PubMed: 9697690, 23083126, 25209843, 24745671, 25504284, 27777718, 16015387, 25355294; OMIM: 164920
EPCAM Heterozygous pathogenic variants in the EPCAM gene cause Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome. PubMed: 20301390, 23462293
SMAD4 Heterozygous pathogenic variants in SMAD4 are associated with Juvenile Polyposis Syndrome (JPS). Biallelic pathogenic variants cause Hereditary Hemorrhagic Telangiectasia (HHT). PubMed: 19553198, 20301642
MAX Autosomal dominant pathogenic variants in the MAX gene have been associated with susceptibility to pheochromocytoma and paraganglioma. Risk for the development of a pheochromocytoma in individuals with germline MAX pathogenic variants is much higher if the variant was paternally inherited. PubMed: 20301715; OMIM: 154950
MC1R Heterozygous variants in MCR1 may lead to an increased susceptibility to hereditary melanoma. However, additional research is needed to confirm this association and further define any associated risks. PubMed: 10631149, 10744096, 16982779, 18366057, 19578364
MEN1 Autosomal dominant pathogenic variants in the gene MEN1 cause Multiple endocrine neoplasia type 1 (MEN1), which is associated with an increased risk for both endocrine and non-endocrine tumors. PubMed: 20301710; OMIM: 131100
MET Heterozygous pathogenic variants in the MET gene have been reported in rare cases of familial papillary renal cell carcinoma, although additional studies are needed given the small number of reported families. PubMed: 24359990, 11551094, 10417759; OMIM: 605074
MITF Heterozygous pathogenic variants in MITF are associated with an increased risk for melanoma, and possibly renal cell carcinoma and others. PubMed: 22012259, 26337759, 28283772
MLH1 While heterozygous pathogenic variants in MLH1 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065; OMIM: 120436
MRE11 Autosomal dominant pathogenic variants in the MRE11 gene, also known as MRE11A, have been associated with a predisposition to breast cancer . Biallelic mutations in the MRE11A gene are associated with MRE11 deficiency, an ataxia telangiectasia-like disorder. PubMed: 26436112, 26328243, 15574463; OMIM: 600814
MSH2 Heterozygous pathogenic variants in MSH2 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome. Biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065; OMIM: 120436
MUTYH Biallelic pathogenic variants in the MUTYH gene cause MUTYH-associated polyposis syndrome (MAP). Heterozygous pathogenic variants in the MUTYH gene may result in a small increased risk for colon cancer. Elevated risk for ovarian cancers have also been reported. PubMed: 16492921, 19394335, 23035301, 23507534
NBN Heterozygous pathogenic variants in NBN (also known as NBS1) have been associated with a number of malignancies including melanoma, non-Hodkins lymphoma, medulloblastoma, and colorectal, prostate, and breast cancers . Other studies have shown possible associations with aplastic anemia and acute lymphoblastic leukemia. Biallelic pathogenic variants in NBN have been associated with Nijmegen Breakage syndrome (NBS). Individuals with NBS generally have progressive intellectual disability, growth retardation and immunodeficiency, and are at an increased risk for a variety of cancers, including lymphoma, glioma, and medulloblastoma. PubMed: 14973119, 15185344, 16474176, 16770759, 18079974, 19908051, 21514219,15338273,11325820, 20301355; OMIM: 609135, 251260
NF1 Autosomal dominant pathogenic variants in NF1 cause Neurofibromatosis Type 1, which is associated with several types of benign tumors and cancer, including neurofibromas, optic glioma, gastrointestinal stromal tumors, plexiform neurofibromas, and malignant peripheral nerve sheath tumors, and breast cancer. PubMed: 17636453, 20301288, 9639526, 27787920; OMIM: 613113
NF2 Heterozygous pathogenic variants in NF2 are associated with Neurofibromatosis, Type 2. Individuals with this condition are at an increased risk for bilateral vestibular schwannomas, as well as other types of tumors. PubMed: 20301380; OMIM: 607379
NTHL1 Biallelic mutations in the base excision repair gene NTHL1 have been associated with familial adenomatous polyposis-3 (FAP3) which is also referred to as NTHL1-associated polyposis (NAP). PubMed: 28331556, 26431160; OMIM: 602656
PDGFRA Heterozygous germline pathogenic variants are a rare cause of Familial Gastrointestinal Stromal Tumor Syndrome. PubMed: 27437068
PMS2 Heterozygous pathogenic variants in PMS2 are associated with Hereditary Nonpolyposis Cancer Syndrome (HNPCC), also known as Lynch syndrome. PMS2 is the least common of the mismatch repair genes that cause HNPCC, accounting for less than 5% of cases. Biallelic pathogenic mutations in PMS2 have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065
POLD1 Heterozygous pathogenic variants in POLD1 have been associated with colorectal cancer and other adenomas including endometrial and breast. PubMed: 24509466, 23263490
POLE Heterozygous pathogenic variants in the POLE gene are associated with early onset colorectal cancer (CRC) and polyposis, also known as Polymerase Proofreading-associated Syndrome (PPAS). Further studies are needed to determine which cancers are directly related to POLE gene variants and the levels of associated risks. Based on the information available today, the risk for colorectal cancer appears to be significantly elevated, and the risk for brain tumors may also be increased . PubMed: 23263490, 26133394; OMIM: 174762
POLH Biallelic pathogenic variants in POLH are associated with xeroderma pigmentosum, which increases the risk for skin cancer. PubMed: 20301575; OMIM: 603968
PRKAR1A Heterozygous pathogenic variants in PRKAR1A are associated with Carney Complex. Individuals with this condition are at an increased risk for thyroid carcinoma, myxoma, Sertoli cell tumors, breast ductal adenoma, and schwannomas. PubMed: 20301463; OMIM: 188830
PRSS1 Heterozygous pathogenic germline variants in PRSS1 are associated with pancreatitis, which increases the risk for pancreatic cancer. PubMed: 22379635; OMIM: 276000
PTCH1 Autosomal dominant pathogenic variants in PTCH1 are associated with Nevoid Basal Cell Carcinoma syndrome (NBCSS), also known as Gorlin syndrome. PubMed: 20301330; OMIM: 601309
PTEN Individuals with heterozygous pathogenic PTEN variants are at a significantly increased risk for multiple types of cancers, including breast, thyroid, colorectal, endometrial, renal, and others. Autosomal dominant mutations in PTEN have been associated with a spectrum of disorders sometimes referred to as PTEN hamartoma tumor syndrome. PHTS includes several conditions with overlapping clinical features, including Bannayan-Riley-Ruvalcaba syndrome (BRRS), Cowden syndrome (CWS1), macrocephaly/autism syndrome, and PTEN-related Proteus syndrome (PS). PubMed: 20301661; OMIM: 601728
RAD51C Heterozygous pathogenic variants in RAD51C are associated with an increased risk for ovarian cancer, and possibly breast cancer. Additionally, biallelic pathogenic variants in RAD51C were reported to be associated with Fanconi anemia. PubMed: 22476429, 22538716, 21990120, 2841844
RAD51D Heterozygous pathogenic variants in RAD51D are associated with an increased risk for breast cancer and ovarian cancer. PubMed: 21822267, 26261251, 2841844
RB1 Heterozygous pathogenic variants in RB1 are association with an increased risk for retinoblastoma, melanoma, and osteo- and soft tissue sarcomas ranging from infancy to 141 months of age. PubMed: 20301625
RET Autosomal dominant pathogenic variants in the RET gene are associatediwth Multiple endocrine neoplasia type 2 (MEN 2), which is associated with medulary thyroid carcinoma, pheochromocytoma, and other clinical findings. PubMed: 20301434; OMIM: 164761
SDHA Autosomal dominant pathogenic variants in SDHA are one genetic cause of Hereditary Paragangliomas-Pheochromocytoma Syndromes (HPPS), and are responsible for approximately .6-3% of cases PubMed: 20301715, 26273102
SDHB Autosomal dominant pathogenic variants in SDHB are one genetic cause of Hereditary Paraganglioma-Pheochromocytoma syndrome (HPPS) and are responsible for approximately 22-38% of cases. They are also associated with Carney-Stratakis syndrome, which is characterized by the presence of paragangliomas and gastrointestinal stromal tumors. SDHB-related HPPS has the highest risk for malignancy in comparison to the different genetic causes of the condition. PubMed: 20301715, 26273102; OMIM: 606864
SDHC Heterozygous pathogenic variants in the SDHC gene are responsible for between 4 and 8% of cases of Hereditary Parganglioma-Pheochromocytoma syndrome (HPPS). PubMed: 20301715; OMIM: 602413
SDHD Autosomal dominant pathogenic variants in the SDHC gene are the most common cause of Hereditary Parganglioma-Pheochromocytoma syndrome (HPPS). Of note, tumor development occurs much more frequently when the pathogenic variant is inherited from the father (paternal origin). PubMed: 20301715; OMIM: 602690
SMARCA4 Autosomal dominant pathogenic variants in SMARCA4 are associated with Rhabdoid Tumor Predisposition Syndrome. This condition is associated with an increased risk for rhabdoid tumors, such as small cell carcinoma of the ovary, hypercalcemic type and rhabdoid tumors of the kidney, as well as schwannomas and others. PubMed: 25494491, 24752781, 24658002
SMARCB1 Heterozygous pathogenic variants in SMARCB1 are associated with familial rhabdoid tumor predisposition syndrome and familial schwannomatosis. PubMed: 26941181; OMIM: 609322
SMARCE1 There is some evidence that heterozygous pathogenic germline variants in SMARCE1 are associated with risk for meningioma. Additional research is needed to confirm this association given the small number of reported cases to date. PubMed: 25249420, 26803492
STK11 Autosomal dominant pathogenic variants in STK11 have been associated with Peutz-Jeghers syndrome (PJS) which is associated with an increased risk for multiple types of cancer, including breast, ovarian, gastric, colorectal, and pancreatic. PubMed: 15121768, 20301443, 24179492; OMIM: 175200, 260350
TERC Autosomal dominant pathogenic variants in TERC have been associated with dyskeratosis congenita, which is associated with squamous cell carcinoma of the head and neck, as well as bone marrow failure PubMed: 20301779
TERT Both heterozygous and biallelic pathogenic variants in TERT have been associated with dyskeratosis congenita, which is associated with squamous cell carcinoma of the head and neck or anogenital region, as well as bone marrow failure, myelodysplastic syndrome, and leukemia. Patients with autosomal dominant (heterozygous) TERT pathogenic variants tend to have milder disease than those with the autosomal recessive (biallelic) form. PubMed: 20301779
TP53 Heterozygous pathogenic variants in the TP53 gene are associated with Li-Fraumeni syndrome, a condition that increases risk for many types of cancer. PubMed: 20301488, 26014290, 2614290; OMIM: 151623, 191170
TSC1 Autosomal dominant pathogenic variants in TSC1 cause Tuberous Sclerosis complex, which is associated with several types of tumors and other clinical conditions. PubMed: 20301399; OMIM: 605284
TSC2 Autosomal dominant pathogenic variants in TSC2 cause Tuberous Sclerosis complex, which is associated with several types of tumors and other clinical conditions. PubMed: 20301399; OMIM: 191092
TYR Biallelic pathogenic variants are associated with oculocutaneous albinism types IA and IB. Heterozygous pathogenic variants in TYR may be associated with a small increased risk for melanoma and basal cell carcinoma. However, this remains controversial and additional research is needed. PubMed: 20301345, 25093188, 18488027, 22464347; OMIM: 203100, 606952
VHL Heterozygous pathogenic variants in VHL cause von Hippel-Lindau (VHL) syndrome, which increases the risk for many types of cancer, including hemangioblastoma, clear cell renal cell carcinoma, pheochromocytoma, and neuroendocrine tumors. PubMed: 20301636, 27114602, 25834951, 24355456
WRN Biallelic pathogenic variants in the gene WRN are associated with Werner syndrome, which is characterized by features of premature aging that includes an increased risk for many types of cancer. At this time, heterozygous carriers of a pathogenic variant in WRN have not been shown to have an increased risk of cancer. PubMed: 20301687, 8722214, 10811130, 20301687; OMIM: 277700
WT1 Autosomal dominant pathogenic variants in the WT1 gene are associated with an increased risk for Wilms tumor. PubMed: 20301471; OMIM: 607102
XPA Biallelic pathogenic variants in XPA are associated with xeroderma pigmentosum, complementation group A, which increases the risk for skin cancer. PubMed: 20301575; OMIM: 611153
XPC Biallelic pathogenic variants in XPC are one of the most common genetic causes of xeroderma pigmentosum, which increases the risk for skin cancer. PubMed: 20301575; OMIM: 613208
XRCC2 Autosomal dominant pathogenic variants in the XRCC2 gene may be associated with an increased risk of breast cancer. Biallelic variants cause Fanconi anemia. PubMed: 22464251, 22232082, 27208205; OMIM: 600375
LZTR1 Autosomal dominant pathogenic variants in LZTR1 are associated with an increased risk for schwannomatosis. PubMed: 24362817, 27921248, 2829512; OMIM: 615670)
AXIN2 Heterozygous pathogenic variants in AXIN2 are associated with Oligodontia-Colorectal Cancer Syndrome (ODCRCS) . ODCRCS is associated with an elevated risk for colorectal (colon) cancer in both men and women, in comparison to the general population, albeit the current elevation in risk remains unkn PubMed: ­­­­­­­­­15042511; OMIM: 608615
BAP1 Heterozygous pathogenic variants in BAP1 are associated with BAP1 tumor predisposition syndrome (BAP1-TPDS). PubMed: 21874003, 23684012, 27748099, 28283772; OMIM: 614327
PTCH2 Heterozygous pathogenic variants in the PTCH2 gene have been reported in a few cases of Nevoid Basal Cell Carcinoma syndrome (NBCSS; also known as Gorlin syndrome). There is also some evidence that autosomal dominant pathogenic variants in PTCH2 are associated with basal cell carcinoma and/or medulloblastoma. Given the small number of reported cases, additional research is needed to confirm these associations and any impact on cancer susceptibility. PubMed: 20301330, 18285427, 9931336; OMIM: 603673
PHOX2B Autosomal dominant pathogenic variants in the PHOX2B gene are associated with familial neuroblastoma. PubMed: 25124476, 28055978
AIP Heterozygous pathogenic variants in AIP are associated with AIP-related familial isolated pituitary adenoma (FIPA), also known as Pituitary Adenoma Predisposition (PAP) syndrome, as well as sporadic pituitary macroadenomas. PubMed: 16728643, 21753072; OMIM: 605555
RECQL4 Biallelic pathogenic mutations in RECQL4 are associated with Rothmund-Thomson syndrome (RTS), Baller-Gerold syndrome (BGS), and RAPADILINO syndrome, which are characterized by growth restriction as well as abnormalities of the bones, skin and gastrointestinal tract. Additionally, affected individuals have an increased risk for developing skin, bone and blood cancers. PubMed: 20301383, 20301415; OMIM: 603780
RAD50 Autosomal dominant pathogenic variants in RAD50 may be associated with a small increased risk for breast cancer, although studies are contradictory. Biallelic pathogenic variants in RAD50 were reported to be associated with Nijmegen breakage syndrome-like disorder (NBSLD) in one individual. PubMed: 19409520, 20301355, 23586058, 26250988, 28418444; OMIM: 613078
HOXB13 Heterozygous pathogenic variants in HOXB13 are associated with an increased risk for prostate cancer. PubMed: 22236224, 24026887, 22841674, 23457453­­­­­­­­­; OMIM: 604607
CHEK2 Heterozygous pathogenic variants in CHEK2 are associated with an increased risk for breast, prostate, colorectal, and thyroid cancer, as well as melanoma. PubMed: 16998506, 18172190, 21876083, 27595995, 15492928, 11719428, 20597917, 21807500, 21876083, 21956126, 23713947, 23296741, 24240112, 24599715, 24879340, 25431674, 28283864
FAN1 Heterozygous pathogenic variants in the FAN1 gene have been associated with Hereditary Non-polyposis Colon Cancer (HNPCC) in a few families. However, additional research is needed to confirm this association. PubMed: 26052075, 27713038
KIF1B There is some evidence that pathogenic variants in KIF1B may be associated with an increased risk for pheochromocytomas and paragangliomas, as well as neuroblastoma. Additional research is needed to confirm these associations and any increased risk for cancer. PubMed: 20301715; OMIM: 605995
DICER1 Autosomal dominant mutations in DICER1 are associated with DICER1 syndrome, a familial tumor susceptibility syndrome which includes susceptibility to many different kinds of tumors. PubMed: 24761742; OMIM: 606241
POT1 Autosomal dominant pathogenic variants in POT1 has been associated with an increased risk for melanoma and gliomas PubMed: 26337759, 28283772, 25482530, 24686846, 27528712, 24686849; OMIM: 606478
TINF2 Autosomal dominant pathogenic variants in TINF2 are associated with dyskeratosis congenita, which increases the risk for bone marrow failure and other malignancies. PubMed: 20301779
GREM1 Duplications upstream from the GREM1 gene have been associated with Hereditary Mixed Polyposis syndrome. PubMed: 22561515, 25992589, 26947005, 28242209; OMIM: 603054
MLH3 Autosomal dominant pathogenic variants in MLH3 have been found in a few families with Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Further studies are needed, however, to confirm the association. PubMed: 11586295, 12702580, 16885347, 20301390; OMIM: 604395
SUFU Autosomal dominant pathogenic variants in SUFU have been associated with Nevoid basal cell Carcinoma syndrome (also called Gorlin syndrome). PubMed: 20301330; OMIM: 607035
EGLN1 There is some evidence that pathogenic variants in EGLN1 may be associated with an increased risk for pheochromocytomas and paragangliomas. The evidence is contradictory. Additional research is needed to confirm this association and any increased risk for cancer. PubMed: 20301715; OMIM: 606425
SDHAF2 Autosomal dominant pathogenic variants in the SDHAF2 gene have been associated with susceptibility to paragangliomas. Risk for developing a paraganglioma in individuals with germline SDHAF2 pathogenic variants is much higher if the variant was paternally inherited, and they most frequently occur in the skull base and neck. PubMed: 20301715; OMIM: 613019
FANCL Biallelic pathogenic variants in FANCL cause Fanconi Anemia, complementation group L. PubMed: 20301575; OMIM: 608111, 614083
WRAP53 Biallelic pathogenic variants in WRAP53 are associated with dyskeratosis congenita, which increases the risk for bone marrow failure and other malignancies. PubMed: 20301779; OMIM: 612661
FANCI Biallelic pathogenic variants in FANCI cause Fanconi Anemia, complementation group I. PubMed: 20301575; OMIM: 611360, 609053
NOP10 Biallelic pathogenic variants in NOP10 are associated with dyskeratosis congenita, which increases the risk for bone marrow failure and other malignancies. PubMed: 20301779; OMIM: 606471
NHP2 Biallelic pathogenic variants in NHP2 are associated with dyskeratosis congenita, which increases the risk for bone marrow failure and other malignancies. PubMed: 20301779; OMIM: 606470
TMEM127 Heterozygous pathogenic variants in the SDHC gene are associated with an increased risk for pheochromocytomas. PubMed: 20301715; OMIM: 613403
FANCM Biallelic pathogenic variants in FANCM may cause Fanconi Anemia, complementation group M, although additional research is needed due to the small number of reported cases. PubMed: 20301575; OMIM: 609644
CDC73 Autosomal dominant pathogenic variants in CDC73 are associated with hyperparathyroidism-jaw tumor syndrome, which increases the risk for renal tumors (hamartomas, Wilms tumor), parathyroid tumors, and ossifying fibromas of the maxilla or mandible. PubMed: 27857527; OMIM: 607393
GALNT12 Heterozygous germline pathogenic variants in GLNT12 may contribute to an increased risk for colorectal cancer; however, additional research is needed to confirm this association and define any related risks. PubMed: 19617566, 22461326, 24115450
PALB2 Autosomal dominant pathogenic variants in PALB2 have been associated with an increased risk of some types of cancer, including breast and pancreatic cancer. Biallelic pathogenic variants in PALB2 have been associated with Fanconi anemia of complementation group N (FANCN) . For women, the risk for breast cancer has been estimated to be two to three times greater than the population risk. PubMed: 17200672, 24870022, 17200668, 21285249, 24141787, 25099575; OMIM: 610355
CTC1 Biallelic pathogenic variants in the CTC1 gene account for approximately 1-3% of cases of dyskeratosis congenita, which increases the risk for bone marrow failure and other malignancies. PubMed: 20301779; 22532422; OMIM: 613129
BRIP1 Heterozygous pathogenic germline variants in the BRIP1 gene are associated with an increased risk for ovarian cancer. Biallelic mutations in BRIP1 have been associated with Fanconi anemia of complementation group J (FANCJ). PubMed: 24301948, 28085182, 20301575; OMIM: 609054, 605882
SLX4 Biallelic pathogenic variants in SLX4 are a rare cause of Fanconi Anemia. Specific increased risks associated with carrying a heterozygous SLX4 variant have not been established at this time. Additional research is needed. PubMed: 21240275, 20301575; OMIM: 613278, 613951
DIS3L2 Biallelic pathogenic variants in DIS3L2 are associated with Perlman syndrome, a congenital overgrowth syndrome associated with approximately a 30% risk to develop Wilms tumor. PubMed: 22306653, 20301471; OMIM: 614184
FLCN Autosomal dominant pathogenic variants in the FLCN gene have been associated with Birt-Hogg-Dube syndrome which is characterized by cutaneous manifestations, spontaneous pneumothorax and renal tumors, including renal cell carcinoma. PubMed: 20301695; OMIM: 607273