• Test code: 08135
  • 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 X-Linked Severe Combined Immunodeficiency (SCID) Test

Test description

The Invitae X-Linked Severe Combined Immunodeficiency (SCID) Test analyzes IL2RG, the only gene known to cause X-linked SCID (severe combined immunodeficiency syndrome), the most common cause of SCID. This X-linked condition affects males and is characterized by severe, recurrent and persistent infections due to near-complete absence of T and natural killer (NK) lymphocytes and nonfunctional B lymphocytes.

Genetic testing of this 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 (1 gene)

X-linked severe combined immunodeficiency (X-SCID)

Gene Disorder Protein name Protein symbol
IL2RG γc deficiency interleukin receptor common gamma chain gamma-c

X-linked severe combined immunodeficiency deficiency (SCID) is an inherited disorder of the immune system that occurs exclusively in males. Boys with X-linked 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 even 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-). Many infants with X-linked SCID develop chronic diarrhea, candidiasis, skin rashes, failure to thrive, and absent tonsils and lymph nodes. Without treatment, males with X-linked SCID usually do not live beyond infancy.

Rarely, affected individuals may have a milder form of disease known as atypical or leaky X-Linked SCID. This is characterized by the presence of T and B cells with little or absent NK cells (T+B+NK-). Clinical symptoms include immune dysregulation, rashes, splenomegaly, gastrointestinal malabsorption, and poor growth.

IL2RG is responsible for 19% of all SCID cases in the U.S. IL2RG is the only gene known to be associated with X-linked SCID. Sequence analysis of IL2RG is estimated to identify a pathogenic variant in approximately 99% of individuals affected with X-linked SCID. An additional 1% of cases are identified by deletion/duplication analysis.

X-SCID is inherited in an X-linked manner. Female carriers of X-SCID are asymptomatic.

A recent large scale newborn screening study has estimated that the prevalence of X-linked SCID in the U.S. is approximately 1 : 300,000.

Testing for the IL2RG gene may be considered in males 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