Invitae Renal/Urinary Tract Cancers Panel


Test description

The Invitae Renal/Urinary Tract Cancers Panel analyzes up to 30 genes associated with an increased lifetime risk of developing cancers of the urinary tract (kidneys, renal pelvis, ureters, bladder, and urethra). These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive panel for hereditary renal/urinary tract cancers. Many of these genes are also associated with an increased risk of other cancer types.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (24 genes)


EPCAM: Analysis is limited to deletion/duplication analysis
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.

Add-on preliminary-evidence genes (6 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


MITF: Analysis is limited to the NM_000248.3:c.952G>A p.Glu318Lys variant.
SDHA: Analysis is limited to sequencing analysis. No clinically-relevant del/dups have been reported.

  • Birt-Hogg-Dubé syndrome (BHD)
  • Lynch syndrome
  • Cowden syndrome
  • Li-Fraumeni syndrome (LFS)
  • Tuberous sclerosis complex (TSC)
  • von Hippel-Lindau syndrome (VHL)
  • WT1-related Wilms tumor
  • Hereditary papillary renal cell carcinoma (HPRCC)
  • Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
  • DICER1 syndrome
  • Perlman syndrome
  • Simpson-Golabi-Behmel syndrome
  • Rhabdoid tumor predisposition syndrome (RTPS)

Most cancers of the renal pelvis, ureter, urethra, and bladder are transitional cell carcinoma while most renal cancers are adenocarcinomas; however, not all urinary tract tumors are malignant. The choice of treatment depends on many factors such as tumor size, number of tumors, if they are bilateral, and whether or not they are causing symptoms.

The general population risk of developing kidney cancer is approximately 1.6%. The lifetime risk of developing bladder cancer is from 1%–3.8%, and approximately 75,000 new cases are diagnosed annually in the United States. While most cases are sporadic and isolated, approximately 5% of urinary tract cancers are hereditary and due to a pathogenic variant—a gene that has been identifiably changed. Unlike sporadic cases, hereditary renal and other urinary tract cancers are often characterized by earlier disease onset and multifocal or bilateral tumors. Further, hereditary urinary tract cancers may also be syndromic and associated with other non-urinary features.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant. For gene-associated cancer risks, see the table below.

GeneConditionRenal cancer riskUrinary tract cancer risk
BAP1 BAP1 hereditary cancer predisposition syndrome 10% (PMID: 26096145) _
CDC73 CDC73-related disorders unknown (PMID: 15579037, 7912571)
CDKN1C Beckwith-Wiedemann syndrome up to 8% (Wilms) (PMID: 12138139) _
DICER1 DICER1 syndrome elevated (PMID: 24481001, 21036787) _
DIS3L2 Perlman syndrome elevated (PMID: 23613427) _
EPCAM Lynch syndrome _ elevated (PMID: 20591884)
FH Hereditary leiomyomatosis and renal cell carcinoma 10%-16% (PMID: 12772087, 15724016) _
FLCN Birt-Hogg-Dube syndrome 16% (PMID: 22146830) _
GPC3 Simpson-Golabi-Behmel syndrome elevated (PMID: 2523897, 16398453) _
MET Hereditary papillary renal cell carcinoma elevated (PMID: 24710684, 26052049) _
MLH1 Lynch syndrome _ elevated (PMID: 20591884)
MSH2 Lynch syndrome _ elevated (PMID: 20591884)
MSH6 Lynch syndrome _ elevated (PMID: 20591884)
PMS2 Lynch syndrome _ elevated (PMID: 20591884)
PTEN Cowden and Cowden-like syndrome elevated (PMID: 22252256) _
SDHB Hereditary paraganglioma-pheochromocytoma syndrome, Carney-Stratakis syndrome elevated (PMID: 18728283, 23083876) _
SDHC Hereditary paraganglioma-pheochromocytoma syndrome, Carney-Stratakis syndrome elevated (PMID: 23083876) _
SMARCA4 Rhabdoid tumor predisposition syndrome unknown (PMID: 25494491) _
SMARCB1 Rhabdoid tumor predisposition syndrome elevated (PMID: 25494491) _
TP53 Li-Fraumeni syndrome elevated (PMID: 2363254, 11219776) elevated (PMID: 20522432)
TSC1 Tuberous sclerosis complex 2%–5% (PMID: 21182496) _
TSC2 Tuberous sclerosis complex 2%–5% (PMID: 21182496) _
VHL von Hippel-Lindau syndrome 24%–45% (PMID: 26279462, 20833335, 21955200) _
WT1 WT1-related conditions elevated (non-syndromic Wilms tumor) (PMID: 12193442, 25688735) _

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.
Unknown: Based on small studies, the risk may possibly be increased, but it is not well described.

Most of the genes on this panel confer an increased risk of developing renal/urinary tract cancers in an autosomal dominant inheritance pattern. Some of the genes have other inheritance patterns:

  • The GPC3 gene has X-linked inheritance.
  • MLH1, MSH2, PMS2 and MSH6 are associated with autosomal recessive constitutional mismatch repair deficiency (CMMR-D).
  • EPCAM is associated with autosomal recessive congenital tufting enteropathy (CTE).

This panel may be considered for individuals whose clinical and family histories are suggestive of a hereditary urinary tract cancer syndrome, including:

  • early onset renal/urinary tract cancer (diagnosed ≤50)
  • multiple primary cancers in one person, one of which is a cancer of the kidney/urinary tract
  • two or more family members with renal/urinary tract cancer

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:
  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both organs of a set of paired organs (e.g., both kidneys)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., breast cancer in a man)

  1. Aarnio, M, et al. Uroepithelial and kidney carcinoma in Lynch syndrome. Fam. Cancer. 2012; 11(3):395-401. PMID: 22476430
  2. Alam, NA, et al. Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome. Arch Dermatol. 2005; 141(2):199-206. PMID: 15724016
  3. Bahubeshi, A, et al. Germline DICER1 mutations and familial cystic nephroma. J. Med. Genet. 2010; 47(12):863-6. doi: 10.1136/jmg.2010.081216. PMID: 21036787
  4. Byler, TK, Bratslavsky, G. Hereditary renal cell carcinoma: genetics, clinical features, and surgical considerations. World J Urol. 2014; 32(3):623-30. doi: 10.1007/s00345-014-1287-4. PMID: 24710684
  5. Courthod, G, et al. Papillary renal cell carcinoma: A review of the current therapeutic landscape. Crit. Rev. Oncol. Hematol. 2015; :None. doi: 10.1016/j.critrevonc.2015.05.008. PMID: 26052049
  6. Devesa, SS, et al. Comparison of the descriptive epidemiology of urinary tract cancers. Cancer Causes Control. 1990; 1(2):133-41. PMID: 2102283
  7. Donahue, HJ, et al. Kinetics of erythrocyte plasma membrane (Ca2+, Mg2+)ATPase in familial benign hypercalcemia. J. Clin. Endocrinol. Metab. 1989; 68(5):893-8. PMID: 2523897
  8. Doros, LA, et al. DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Mod. Pathol. 2014; 27(9):1267-80. PMID: 24481001
  9. Evenepoel, L, et al. Toward an improved definition of the genetic and tumor spectrum associated with SDH germ-line mutations. Genet. Med. 2014; :None. PMID: 25394176
  10. Goldman, M, et al. Renal abnormalities in beckwith-wiedemann syndrome are associated with 11p15.5 uniparental disomy. J. Am. Soc. Nephrol. 2002; 13(8):2077-84. PMID: 12138139
  11. Gontar', IP, et al. [The use of immobilized granulated G-actin with magnetic properties in patients and experimental animals]. Vopr. Med. Khim. 1990; 36(2):28-9. PMID: 2363254
  12. Gracia, Bouthelier, R, Lapunzina, P. Follow-up and risk of tumors in overgrowth syndromes. J. Pediatr. Endocrinol. Metab. 2005; 18 Suppl 1:1227-35. PMID: 16398453
  13. Hampel, H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet. Med. 2015; 17(1):70-87. doi: 10.1038/gim.2014.147. PMID: 25394175
  14. Hegde, MR, Roa, BB. Genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC). Curr Protoc Hum Genet. 2009; Chapter 10:Unit 10.12. doi: 10.1002/0471142905.hg1012s61. PMID: 19360696
  15. Houweling, AC, et al. Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. Br. J. Cancer. 2011; 105(12):1912-9. doi: 10.1038/bjc.2011.463. PMID: 22146830
  16. Kakinuma, A, et al. Familial primary hyperparathyroidism complicated with Wilms' tumor. Intern. Med. 1994; 33(2):123-6. PMID: 7912571
  17. Kaneko, Y, et al. A high incidence of WT1 abnormality in bilateral Wilms tumours in Japan, and the penetrance rates in children with WT1 germline mutation. Br. J. Cancer. 2015; 112(6):1121-33. PMID: 25688735
  18. Mork, M, et al. Lynch Syndrome: A Primer for Urologists and Panel Recommendations. J. Urol. 2015; 194(1):21-9. PMID: 25711197
  19. Morris, MR, et al. Perlman syndrome: overgrowth, Wilms tumor predisposition and DIS3L2. Am J Med Genet C Semin Med Genet. 2013; 163C(2):106-13. PMID: 23613427
  20. Nichols, KE, et al. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol. Biomarkers Prev. 2001; 10(2):83-7. PMID: 11219776
  21. Pritchard-Jones, K. Controversies and advances in the management of Wilms' tumour. Arch. Dis. Child. 2002; 87(3):241-4. PMID: 12193442
  22. Rai, K, et al. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin. Genet. 2015. PMID: 26096145
  23. Ruijs, MW, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J. Med. Genet. 2010; 47(6):421-8. PMID: 20522432
  24. Skeldon, SC, et al. Patients with Lynch syndrome mismatch repair gene mutations are at higher risk for not only upper tract urothelial cancer but also bladder cancer. Eur. Urol. 2013; 63(2):379-85. PMID: 22883484
  25. Sredni, ST, Tomita, T. Rhabdoid tumor predisposition syndrome. Pediatr. Dev. Pathol. 2015; 18(1):49-58. doi: 10.2350/14-07-1531-MISC.1. PMID: 25494491
  26. Tan, MH, Teh, BT. Renal neoplasia in the hyperparathyroidism-jaw tumor syndrome. Curr. Mol. Med. 2004; 4(8):895-7. PMID: 15579037
  27. Tan, MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin. Cancer Res. 2012; 18(2):400-7. doi: 10.1158/1078-0432.CCR-11-2283. PMID: 22252256
  28. Toro, JR, et al. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am. J. Hum. Genet. 2003; 73(1):95-106. PMID: 12772087
  29. Win, AK, et al. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J. Clin. Oncol. 2012; 30(9):958-64. PMID: 22331944
  30. Wind, JJ, Lonser, RR. Management of von Hippel-Lindau disease-associated CNS lesions. Expert Rev Neurother. 2011; 11(10):1433-41. doi: 10.1586/ern.11.124. PMID: 21955200
  31. van, der, Post, RS, et al. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J. Med. Genet. 2010; 47(7):464-70. PMID: 20591884

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
BAP1 NM_004656.3
BUB1B NM_001211.5
CDC73 NM_024529.4
CDKN1C NM_000076.2
CEP57 NM_014679.4
DICER1 NM_177438.2
DIS3L2 NM_152383.4
EPCAM* NM_002354.2
FH NM_000143.3
FLCN NM_144997.5
GPC3 NM_004484.3
MET NM_001127500.1
MITF* NM_000248.3
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6 NM_000179.2
PALB2 NM_024675.3
PMS2 NM_000535.5
PTEN* NM_000314.4
SDHA* NM_004168.3
SDHB NM_003000.2
SDHC NM_003001.3
SDHD NM_003002.3
SMARCA4 NM_001128849.1
SMARCB1 NM_003073.3
TP53* NM_000546.5
TSC1 NM_000368.4
TSC2 NM_000548.3
VHL NM_000551.3
WT1 NM_024426.4

EPCAM: Analysis is limited to deletion/duplication analysis
MITF: Analysis is limited to the NM_000248.3:c.952G>A p.Glu318Lys variant.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PTEN: Deletion/duplication analysis covers the promoter region.
SDHA: Analysis is limited to sequencing analysis. No clinically-relevant del/dups have been reported.
TP53: Deletion/duplication analysis covers the promoter region.