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  • Test code: 08137
  • 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 Combined Immunodeficiency (CID) Panel

Test description

The Invitae Combined Immunodeficiency (CID) Panel analyzes up to 69 genes that are associated with SCID and CID. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.

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Primary panel (33 genes)

B2M BCL10 CARD11 CD27 CD3G CD40LG CD8A CIITA CTPS1 DOCK2 DOCK8 ICOS IKBKB IL21 IL21R ITK LCK LRBA MAGT1 MALT1 MAP3K14 RAC2 RFX5 RFXANK RFXAP RHOH SH2D1A STK4 TAP1 TAP2 TAPBP TNFRSF4 ZAP70

Add-on Combined Immunodeficiencies (CID) with Syndromic Features (39 genes)

Combined immunodeficiencies (CID) with syndromic features have significant overlap of immunological findings compared to patients with non-syndromic CID. Especially at very early ages, some syndromic features may be difficult to identify or have not yet manifested. Given the significant overlap between syndromic and non-syndromic CID and the difficulty in differentiating between the syndromic and non-syndromic forms early in life, analyzing the genes associated with syndromic CID may be appropriate. These genes can be included at no additional charge.

ACD ACD ATM CHD7 CTC1 DCLRE1B DKC1 DNMT3B EPG5 FOXN1 NBN NFKBIA NHP2 NOP10 ORAI1 PARN PARN PGM3 PMS2 POLE RMRP RTEL1 RTEL1 SEMA3E SMARCAL1 SP110 SPINK5 STAT3 STAT5B STIM1 TBX1 TCN2 TERC TERT TINF2 TTC7A WAS WIPF1 ZBTB24

Alternative tests to consider

For a broader analysis of the genetics of combined immunodeficiency syndromes:



Gene Disorder Protein name Protein symbol
B2M MHC class I deficiency Beta-2-microglobulin B2M
BCL10 BCL10 deficiency B cell CLL / lymphoma 10 protein BCL10
CARD11 CARD11 deficiency, CARD11 gain of function caspase recruitment domain-containing protein 11 CARD11
CD27 CD27 deficiency CD27 antigen CD27
CD3G CD3γ deficiency CD3-gamma CD3-gamma
CD40LG CD40 ligand deficiency CD40 ligand CD40LG
CD8A CD8 deficiency CD8-alpha chain CD8
CIITA MHC class II deficiency MHC class II transactivator CIITA
CTPS1 CTPS1 deficiency CTP synthase CTPS1
DOCK2 DOCK2 deficiency dedicator of cytokinesis 2 DOCK2
DOCK8 DOCK8 deficiency dedicator of cytokinesis 8 DOCK8
ICOS ICOS deficiency inducible T-cell costimulator ICOS
IKBKB IKBKB deficiency I-kappa-B kinase 2 IKK2
IL21 IL-21 deficiency IL-21 deficiency IL-21
IL21R IL-21R deficiency interleukin-21 receptor IL-21R
ITK lymphoproliferative syndrome type 1 (LPFS1) interleukin 2 inducible T-cell kinase ITK
LCK LCK deficiency lymphocyte-specific protein-tyrosine kinase p56(LCK)
LRBA LRBA deficiency lipopolysaccharide responsive beige-like anchor protein LRBA
MAGT1 X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN) magnesium transporter 1 MAGT1
MALT1 MALT1 deficiency mucosa-associated lymphoid tissue lymphoma translocation gene 1 MALT1
MAP3K14 NIK deficiency NF-kB-inducing kinase NIK
RAC2 Rac 2 deficiency rho family small GTP-binding protein RAC2 RAC2
RFX5 MHC class II deficiency group C regulatory factor X5 RFX5
RFXANK MHC class II deficiency group B regulatory factor X, ankyrin repeat-containing RFXANK
RFXAP MHC class II deficiency group D regulatory factor X associated protein RFXAP
RHOH RhoH deficiency ras homolog gene family member H RHOH
SH2D1A SH2D1A deficiency (XLP1) SH2 domain protein 1A SH2D1A
STK4 MST1 deficiency mammalian sterile 20-like 1 MST1
TAP1 MHC class I deficiency ABC transporter MHC 1 TAP1
TAP2 MHC class I deficiency ABC transporter MHC 2 TAP2
TAPBP MHC class I deficiency tapasin TPSN
TBX1 DiGeorge syndrome T-box 1 TBX1
TNFRSF4 OX40 deficiency OX40 antigen OX40
ZAP70 ZAP-70 deficiency protein tyrosine kinase ZAP70 ZAP70

Combined immunodeficiency syndromes (CIDs) are a heterogenous group of primary immunodeficiencies that are generally less profound than SCID. Similar to SCID, CID results in the dysfunction of T-lymphocytes and to a variable extent B-lymphocytes and/or N-lymphocytes. These patients tend to have higher numbers of circulating autologous T cells compared with SCID patients. CID patients are still susceptible to frequent infections that may be hard to treat, but they are typically less severe than those seen in SCID. Other features may include failure to thrive and skin involvement such as recurrent skin infections or rashes, granuloma, and increased risk of malignancy. Patients often present after 1 year of life. Many patients have been treated with hematopoietic stem cell transplant.

The clinical sensitivity of this test is dependent on the patient’s underlying genetic condition. This test covers the vast majority of CID but the exact clinical sensitivity of this test is unknown.

CIDs can be inherited in several patterns, including autosomal dominant, autosomal recessive, and X-linked.

The incidence for the CID as a whole is not known as these conditions are likely underdiagnosed.

This test may be considered for individuals:

  • who have abnormal newborn screening results for SCID
  • who have combined immunodeficiency in peripheral blood
  • who have a history of severe early-onset infections, and trisomy 21, trisomy 18, and other microdeletion syndromes have been ruled out

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
ACD NM_001082486.1
ACD NM_001082486.1
ATM NM_000051.3
B2M NM_004048.2
BCL10 NM_003921.4
CARD11 NM_032415.5
CD27 NM_001242.4
CD3G NM_000073.2
CD40LG NM_000074.2
CD8A NM_001768.6
CHD7 NM_017780.3
CIITA NM_000246.3
CTC1 NM_025099.5
CTPS1 NM_001905.3
DCLRE1B NM_022836.3
DKC1 NM_001363.4
DNMT3B NM_006892.3
DOCK2 NM_004946.2
DOCK8 NM_203447.3
EPG5 NM_020964.2
FOXN1 NM_003593.2
ICOS NM_012092.3
IKBKB NM_001556.2
IL21 NM_021803.3
IL21R NM_021798.3
ITK NM_005546.3
LCK NM_001042771.2
LRBA NM_006726.4
MAGT1 NM_032121.5
MALT1 NM_006785.3
MAP3K14 NM_003954.4
NBN NM_002485.4
NFKBIA NM_020529.2
NHP2 NM_017838.3
NOP10 NM_018648.3
ORAI1 NM_032790.3
PARN NM_002582.3
PARN NM_002582.3
PGM3 NM_001199917.1
PMS2 NM_000535.5
POLE NM_006231.3
RAC2 NM_002872.4
RFX5 NM_000449.3
RFXANK NM_003721.3
RFXAP NM_000538.3
RHOH NM_004310.4
RMRP NR_003051.3
RTEL1 NM_001283009.1
RTEL1 NM_001283009.1
SEMA3E NM_012431.2
SH2D1A NM_002351.4
SMARCAL1 NM_014140.3
SP110 NM_004509.3
SPINK5 NM_006846.3
STAT3 NM_139276.2
STAT5B NM_012448.3
STIM1 NM_003156.3
STK4 NM_006282.3
TAP1 NM_000593.5
TAP2 NM_000544.3
TAPBP NM_003190.4
TBX1 NM_080647.1
TCN2 NM_000355.3
TERC NR_001566.1
TERT NM_198253.2
TINF2 NM_001099274.1
TNFRSF4 NM_003327.3
TTC7A NM_020458.3
WAS NM_000377.2
WIPF1 NM_001077269.1
ZAP70 NM_001079.3
ZBTB24 NM_014797.2