• Test code: 08133
  • 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

Invitae T-B+NK- Severe Combined Immunodeficiency (SCID) Panel

Test description

The Invitae T-B+NK- Severe Combined Immunodeficiency (SCID) Panel analyzes 2 genes that are associated with severe combined immunodeficiency which typically present with a lymphocyte profile of T-B+NK-.

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.

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Primary panel (2 genes)

T-cell negative, B-cell positive, NK-cell negative severe combined immunodeficiency (SCID) including:

Gene Disorder Protein name Protein symbol
IL2RG γc deficiency interleukin receptor common gamma chain gamma-c
JAK3 JAK3 deficiency Janus activating kinase 3 JAK3

Severe combined immunodeficiency (SCID) is an infantile-onset primary immunodeficiency in which there is dysfunction of both of T-cells and B-cells. Individuals with JAK3- and IL2RG-related SCID appear normal at birth. However, as maternal antibodies decline, they become increasingly prone to severe recurrent and persistent infections due to lack of the necessary immune cells to fight ordinary contagions. The typical laboratory profile includes near-absent peripheral T and natural killer (NK) cells, and a normal number of nonfunctional B lymphocytes (T-B+NK-). SCID is characterized by recurrent, overwhelming viral, bacterial and fungal infections and failure to thrive, which if untreated often lead to early death.

JAK3- and IL2RG-related SCID are clinically indistinguishable, however both males and females can be affected with JAK3-related SCID. To date, heterozygous female carriers of IL2RG-related SCID have not been reported to be affected.

A milder form of IL2RG-related SCID can occur and is known as atypical or leaky X-SCID. This is characterized by the presence of T and B cells with little or absent NK cells. Clinical symptoms include immune dysregulation, rashes, splenomegaly, gastrointestinal malabsorption, and poor growth.

Approximately 19% and 2% of all severe combined immunodeficiencies are due to pathogenic variants in the IL2RG and JAK3 genes, respectively.

Sequence analysis of IL2RG identifies a pathogenic variant in approximately 99% of affected individuals with X-linked SCID. An additional 1% of cases are identified by deletion/duplication analysis.

JAK3-related SCID is inherited in an autosomal recessive pattern. IL2RG-related SCID is inherited in an X-linked pattern.

The prevalence of X-linked SCID in the U.S. is approximately 1 : 300,000 while the prevalence of JAK3-related SCID is approximately 1 in 1,000,000.

Testing for the T-B+NK- SCID panel may be considered in males or females with:

  • low T-cell receptor excision circles (TRECs) on newborn screening
  • lymphocytopenia and/or T-cell (CD3+) lymphopenia
  • severe defect in T-cell proliferation to the mitogen PHA
  • marked decrease in thymic function
  • absent thymic shadow on chest radiogram
  • decreased IL-21-induced STAT3 phosphorylation on functional testing
  • negative HIV viral load testing (RNA/DNA assay)
  • recurrent fevers
  • failure to thrive (FTT)
  • chronic diarrhea
  • recurrence of severe episodes of thrush, mouth ulcers, respiratory syncytial virus (RSV), herpes simplex virus (HSV), varicella zoster virus (VZV), measles, influenza, or parainfluenza 3
  • adverse reactions caused by live vaccines
  • family history of SCID

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
IL2RG NM_000206.2
JAK3 NM_000215.3