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  • Test code: 08130
  • 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 Comprehensive Severe Combined Immunodeficiency (SCID) and Combined Immunodeficiency (CID) Panel

Test description

The Invitae Comprehensive Severe Combined Immunodeficiency (SCID) and Combined Immunodeficiency (CID) Panel analyzes up to 86 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 (50 genes)

ADA AK2 B2M BCL10 CARD11 CD247 CD27 CD3D CD3E CD3G CD40LG CD8A CIITA CORO1A CTPS1 DCLRE1C DOCK2 DOCK8 ICOS IKBKB IL21 IL21R IL2RG IL7R ITK JAK3 LCK LIG4 LRBA MAGT1 MALT1 MAP3K14 NHEJ1 PNP PRKDC PTPRC RAC2 RAG1 RAG2 RFX5 RFXANK RFXAP RHOH SH2D1A STK4 TAP1 TAP2 TAPBP TNFRSF4 ZAP70

Add-on Combined Immunodeficiency (CID) with Syndromic Features Genes (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 primary immunodeficiencies:



Gene Disorder Protein name Protein symbol
ADA Adenosine deaminase (ADA) deficiency adenosine deaminase ADA
AK2 Reticular dysgenesis, AK2 deficiency adenylate kinase-2 AK2
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
CD247 CD3ζ deficiency CD3-zeta CD3-zeta
CD27 CD27 deficiency CD27 antigen CD27
CD3D CD3δ deficiency CD3-delta CD3-delta
CD3E CD3ε deficiency CD3-epsilon CD3-epsilon
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
CORO1A Coronin-1A deficiency coronin-1A CORO1A
CTPS1 CTPS1 deficiency CTP synthase CTPS1
DCLRE1C DCLRE1C (Artemis) deficiency Artemis Artemis
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
IL2RG γc deficiency interleukin receptor common gamma chain gamma-c
IL7R IL7Rα deficiency interleukin 7 receptor alpha IL-7RA
ITK lymphoproliferative syndrome type 1 (LPFS1) interleukin 2 inducible T-cell kinase ITK
JAK3 JAK3 deficiency Janus activating kinase 3 JAK3
LCK LCK deficiency lymphocyte-specific protein-tyrosine kinase p56(LCK)
LIG4 DNA ligase IV deficiency DNA ligase IV LIG4
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
NHEJ1 Cernunnos/XLF deficiency Cernunnos Cernunnos
PNP Purine nucleoside phosphorylase (PNP) deficiency purine nucleoside phosphorylase PNP
PRKDC DNA PKcs deficiency DNA-PKcs DNA-PKcs
PTPRC CD45 deficiency CD45 CD45
RAC2 Rac 2 deficiency rho family small GTP-binding protein RAC2 RAC2
RAG1 RAG 1 deficiency recombinase activating gene 1 RAG1
RAG2 RAG 2 deficiency recombinase activating gene 2 RAG2
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
TNFRSF4 OX40 deficiency OX40 antigen OX40
ZAP70 ZAP-70 deficiency protein tyrosine kinase ZAP70 ZAP70

Severe combined immunodeficiency syndrome (SCID) is an infantile-onset primary immunodeficiency syndrome that results in the dysfunction of T-lymphocytes and B-lymphocytes. Some causes of SCID may also result in defective natural killer cell function. Combined immunodeficiency syndrome (CID) is a primary immunodeficiency that is generally less severe than SCID.

Children with SCID often present with severe, recurrent, and often life-threatening infections that are difficult to treat due to the patient’s compromised immune system. These infections may be caused by opportunistic organisms that are not usually infectious to children with normal immune systems; they can even be caused by vaccines made with a live virus. Patients often have persistent diarrhea, which can lead to a failure to thrive and skin involvement such as recurrent skin infections or rashes. Some patients with milder mutations in SCID-associated genes may be characterized as Omenn syndrome. Patients with Omenn syndrome develop erythroderma, hepatosplenomegaly, and lymphadenopathy in addition to immunodeficiency, and may have T-cells that function poorly. Without treatment, patients with SCID often die early in life, so early diagnosis and treatment are crucial. Patients with CID have similar symptoms to patients with SCID, however, symptoms may be milder. These patients are still susceptible to recurrent life threatening infections. Many patients have been treated successfully with hematopoietic stem cell transplant.

Many states have implemented newborn screening for SCID. Sometimes, patients with CID can also be picked up on newborn screening due to a reduction in T-cell excision circles (TRECs).

The clinical sensitivity of this test is dependent on the patient’s underlying genetic condition. This test covers all of the known genetic causes of SCID and the vast majority of CID. A minimum of 81% of individuals with characteristic features of SCID are expected to have a pathogenic variant(s) identified in one of the genes on this panel, although exact estimates are unknown. The clinical sensitivity of this test for CID is unknown.

Many forms of SCID and CID are autosomal recessive, though the most common cause of SCID is inherited in an X-linked manner. CD40 ligand deficiency and XMEN disease are also inherited in an X-linked recessive manner. RAC2-associated neutrophil immunodeficiency syndrome and DiGeorge syndrome are inherited in an autosomal dominant manner.

According to recent newborn screening data, SCID has an estimated overall incidence rate of 1 in 58,000 in the US. Incidence is as high as 1 in 3,500 in individuals of Navajo heritage due to a founder mutation in DCLRE1C (PMID: 25138334). The incidence for the CID as a whole is not known as these conditions are likely underdiagnosed. However, collectively they are much more common than SCID.

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, but 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
ADA NM_000022.2
AK2 NM_001625.3
ATM NM_000051.3
B2M NM_004048.2
BCL10 NM_003921.4
CARD11 NM_032415.5
CD247 NM_198053.2
CD27 NM_001242.4
CD3D NM_000732.4
CD3E NM_000733.3
CD3G NM_000073.2
CD40LG NM_000074.2
CD8A NM_001768.6
CHD7 NM_017780.3
CIITA NM_000246.3
CORO1A* NM_007074.3
CTC1 NM_025099.5
CTPS1 NM_001905.3
DCLRE1B NM_022836.3
DCLRE1C NM_001033855.2
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
IL2RG NM_000206.2
IL7R NM_002185.3
ITK NM_005546.3
JAK3 NM_000215.3
LCK NM_001042771.2
LIG4 NM_002312.3
LRBA NM_006726.4
MAGT1 NM_032121.5
MALT1 NM_006785.3
MAP3K14 NM_003954.4
NBN NM_002485.4
NFKBIA NM_020529.2
NHEJ1 NM_024782.2
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
PNP NM_000270.3
POLE NM_006231.3
PRKDC NM_006904.6
PTPRC NM_002838.4
RAC2 NM_002872.4
RAG1 NM_000448.2
RAG2 NM_000536.3
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

CORO1A: Deletion/duplication and sequencing analysis is not offered for exon 11 (NM_007074.3).