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  • Test code: 08143
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Mendelian Susceptibility to Mycobacterial Disease Panel

Test description

The Invitae Mendelian Susceptibility to Mycobacterial Disease Panel analyzes 11 genes associated with an inherited susceptibility to develop localized or systemic infection of mycobacteria or other pathogens. This panel may be appropriate for individuals who develop unexpected mycobacterial or other infections. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Genetic testing of these genes may confirm predisposition to certain bacterial and other infections. Diagnosis may help guide treatment and management decisions including therapy and screening. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (11 genes)

CYBB GATA2 IFNGR1 IFNGR2 IL12B IL12RB1 IRF8 ISG15 STAT1 STAT2 TYK2

Alternative tests to consider

For a broader analysis of the genetics of primary immunodeficiencies:



Gene Disorder Protein name Protein symbol
CYBB X-linked chronic granulomatous disease (CGD) 91kD-phagocyte oxidase p91-phox
GATA2 GATA2 deficiency GATA-binding protein 2 GATA2
IFNGR1 IFN-γ receptor 1 deficiency interferon-gamma receptor 1 IFN-gamma R1
IFNGR2 IFN-γ receptor 2 deficiency interferon-gamma receptor 2 IFN-gamma R2
IL12B IL-12p40 deficiency interleukin-12 p40 subunit IL-12p40
IL12RB1 IL-12 and IL-23 receptor β1 chain deficiency interleukin-12 and interleukin-23 receptor beta1 chain IL-12 and IL-23 receptor β1 chain
IRF8 IRF8 deficiency interferon regulatory factor 8 IRF8
ISG15 ISG15 deficiency ubiquitin-like modifier ISG15 ISG15
STAT1 STAT1 deficiency signal transducer and activator of transcription 1 STAT1
STAT2 STAT2 deficiency signal transducer and activator of transcription 2 STAT2
TYK2 Tyk2 deficiency tyrosine kinase 2 TYK2

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition in which affected individuals have impaired immunity resulting in increased likelihood of developing mycobacterial, and less frequently, other types of infections. Infections are often severe, may be systemic or localized, and can be caused by pathogens with varying degrees of virulence including weakly virulent mycobacteria such as environmental nontuberculous mycobacteria and bacillus Calmette-Guérin (BCG) vaccines to Mycobacterium tuberculosis. Other pathogens may include salmonella, listeria, candida, fungi and viruses.

Malignancies including B-cell lymphoma, esophageal carcinoma, cutaneous squamous cell carcinoma, Kaposi sarcoma, liver cancer, and pineal germinoma have also been reported in affected individuals.

Affected individuals typically do not have other health problems and routine hematologic and immunologic tests may be normal. Presentation typically occurs in childhood and more rarely in adolescence or adulthood. Some genetically predisposed individuals will remain asymptomatic.

The clinical sensitivity for this test is unknown. The percentage of patients with MSMD and a pathogenic variant in one of the genes offered in this panel has not been determined.

MSMD is inherited in an autosomal recessive, autosomal dominant or X-linked recessive manner. Some genes are associated with more than one mode of inheritance.

MSMD is thought to be a rare condition. However, its prevalence is not well established.

  1. Qu, HQ, et al. Molecular immunity to mycobacteria: knowledge from the mutation and phenotype spectrum analysis of Mendelian susceptibility to mycobacterial diseases. Int. J. Infect. Dis. 2011; 15(5):e305-13. PMID: 21330176
  2. Bustamante, J, et al. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity. Semin. Immunol. 2014; 26(6):454-70. PMID: 25453225
  3. Casanova, JL, et al. Idiopathic disseminated bacillus Calmette-Guérin infection: a French national retrospective study. Pediatrics. 1996; 98(4 Pt 1):774-8. PMID: 8885960
  4. Chapgier, A, et al. Novel STAT1 alleles in otherwise healthy patients with mycobacterial disease. PLoS Genet. 2006; 2(8):e131. PMID: 16934001
  5. Bax, HI, et al. B-cell lymphoma in a patient with complete interferon gamma receptor 1 deficiency. J. Clin. Immunol. 2013; 33(6):1062-6. PMID: 23800860
  6. Toyoda, H, et al. Multiple cutaneous squamous cell carcinomas in a patient with interferon gamma receptor 2 (IFN gamma R2) deficiency. J. Med. Genet. 2010; 47(9):631-4. PMID: 20587411
  7. Cárdenes, M, et al. Oesophageal squamous cell carcinoma in a young adult with IL-12R beta 1 deficiency. J. Med. Genet. 2010; 47(9):635-7. PMID: 20798129
  8. Camcioglu, Y, et al. HHV-8-associated Kaposi sarcoma in a child with IFNgammaR1 deficiency. J. Pediatr. 2004; 144(4):519-23. PMID: 15069403
  9. Taramasso, L, et al. Pineal germinoma in a child with interferon-γ receptor 1 deficiency. case report and literature review. J. Clin. Immunol. 2014; 34(8):922-7. PMID: 25216720

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CYBB NM_000397.3
GATA2 NM_032638.4
IFNGR1 NM_000416.2
IFNGR2 NM_005534.3
IL12B NM_002187.2
IL12RB1 NM_005535.2
IRF8 NM_002163.2
ISG15 NM_005101.3
STAT1 NM_007315.3
STAT2 NM_005419.3
TYK2 NM_003331.4