Hereditary Renal Cancer Panel

Pathogenic variants in multiple genes have been implicated in hereditary renal cancer. Hereditary cancer predisposition is often characterized by early age of onset (typically before 50 years) and multiple, multifocal, and/or similar cancers in a single individual or in a closely related family member(s). Pathogenic variants in the genes analyzed by this panel cause variable phenotypes and cancer risks, including nonrenal cancers.

Etiology

Approximately 5% of renal cancers are associated with a hereditary cause.

Inheritance

• All genes tested on the Hereditary Renal Cancer Panel are autosomal dominant with the exception of the SDHD gene, which is autosomal dominant with paternal parent-of-origin effect.
• Some genes are also associated with autosomal recessive childhood cancer predisposition or other syndromes.
• See table below for additional details.

See Genes Tested table for genes included in the panel.

Clinical Sensitivity

Variable, dependent on phenotype/condition

Testing Strategy

Contraindications for Ordering

• Should not be ordered to detect somatic variants associated with malignancy as sensitivity for mosaic variants is low with methodology used for germline assays
• Individuals with hematological malignancy and/or a previous allogenic bone marrow transplant should not undergo molecular genetic testing on peripheral blood specimen.
  • Testing of cultured fibroblasts is required for accurate interpretation of test results.
• When a relative has a previously identified pathogenic variant, see Familial Mutation, Targeted Sequencing (2001961).

Limitations

• A negative result does not exclude a heritable form of cancer.
• Diagnostic errors can occur due to rare sequence variations.
• Interpretation of this test result may be impacted if this individual has had an allogeneic stem cell transplantation.
• The following will not be evaluated:
  • Variants outside the coding regions and intron-exon boundaries of the targeted genes
  • Regulatory region variants and deep intronic variants
  • Breakpoints of large deletions/duplications
  • Deletions/duplications in SMARCA4 and WT1
  • Noncoding transcripts
  • The following exons are not sequenced due to technical limitations of the assay:
    • SDHC (NM_001035511) 5
    • SDHD (NM_001276506) 4
• The following may not be detected:
  • Deletions/duplications/insertions of any size by massively parallel sequencing
  • Deletions/duplications less than 1kb in the targeted genes by array
  • Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions
  • Low-level somatic variants
  • Single exon deletions/duplications in the following exons:
    • BAP1 (NM_004656) 1
    • FH (NM_000143) 1
    • FLCN (NM_144997) 8
    • MSH2 (NM_000251) 1; (NM_001258281) 2
    • MSH6 (NM_000179) 10
    • PTEN (NM_000314) 8, 9; (NM_001304717) 1
    • SDHD (NM_001276506) 4
    • SMARCB1 (NM_003073) 5
    • TP53 (NM_001126113) 10; (NM_001126114) 10
    • TSC2 (NM_000548) 17, 29, 41
    • VHL (NM_000551) 1

For massively parallel sequencing:

Genes Tested