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  • Test code: 08150
  • 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 Monogenic Autoimmunity Panel

Test description

The Invitae Monogenic Autoimmunity Panel analyzes 109 genes that are associated with Mendelian disorders of autoimmunity. 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 (75 genes)

ACP5 ADA2 ADAR AICDA AIRE AP3B1 BLOC1S6 BTK CASP10 CASP8 CD27 CD40LG CR2 CTLA4 CYBA CYBB DOCK8 FADD FAS FASLG FOXP3 ICOS IFIH1 IL10 IL10RA IL10RB IL21 IL21R IL2RA ITCH ITK LRBA LYST MAGT1 NCF2 NCF4 NFAT5 NFKB2 NFKBIA ORAI1 PIK3CD PIK3R1 PLCG2 PNP PRF1 PRKCD RAB27A RAC2 RFX5 RFXANK RFXAP RMRP RNASEH2A RNASEH2B RNASEH2C SAMHD1 SH2D1A SLC7A7 STAT1 STAT3 STAT5B STIM1 STX11 STXBP2 TBX1 TMEM173 TNFRSF13B TNFRSF13C TNFSF12 TPP2 TREX1 UNC13D UNG WAS XIAP

Add on Autoinflammatory Syndrome Genes (34 genes)

Generally, autoimmune disorders are caused by defects in adaptive immunity leading to loss of tolerance to self-tissues, whereas autoinflammatory disorders are characterized by episodes of inflammation due to inappropriate activation of the innate immune response. Autoimmune and autoinflammatory diseases share clinical manifestations and some conditions that were once considered autoimmune are now recognized as autoinflammatory in nature (PMID: 24164192). Both types of conditions result in self-directed inflammation in the absence of a known trigger, and recent studies suggest considerable overlap in molecular pathways involved in both groups of conditions (PMID: 29099860). Genes associated with autoinflammatory disorders can be added to this panel at no additional charge.

ADA ADAM17 CARD14 CD3G COPA DCLRE1C DKC1 ELANE G6PC3 IL1RN IL2RG IL36RN ITGB2 LIG4 LPIN2 MEFV MVK NLRC4 NLRP12 NLRP3 NOD2 PSMB8 PSTPIP1 RAG1 RAG2 RBCK1 RTEL1 SH3BP2 SLC29A3 SLC37A4 TNFRSF1A TRNT1 TTC7A ZAP70

Alternative tests to consider

For a broader analysis of the genetics of primary immunodeficiencies:

Gene Disorder Protein name Protein symbol
ACP5 Spondyloenchondro-dysplasia with immune dysregulation tartrate-resistant acid phosphatase TRAP
ADA2 ADA2 deficiency cat eye syndrome chromosome region, candidate 1 CECR1
ADAR ADAR1 deficiency, Aicardi-Goutieres syndrome 6 RNA-specific adenosine deaminase ADAR
AICDA AID deficiency activation-induced cytidine deaminase AID
AIRE APECED (APS-1), autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy autoimmune regulator AIRE
AP3B1 Hermansky-Pudlak syndrome, type 2 adaptor-related protein complex-3, B1 subunit AP3B1
BLOC1S6 Hermansky-Pudlak syndrome, type 9 palladin PLDN
BTK BTK deficiency Bruton agammaglobulinemia tyrosine kinase BTK
CASP10 ALPS-Caspase10 caspase-10 CASP10
CASP8 ALPS IIb, caspase 8 deficiency caspase-8 CASP8
CD27 CD27 deficiency CD27 antigen CD27
CD40LG CD40 ligand deficiency CD40 ligand CD40LG
CR2 CD21 deficiency CD21 CD21
CTLA4 CTLA4 deficiency (ALPSV) Cytotoxic T Lymphocyte antigen 4 CTLA4
CYBA Autosomal recessive CGD 22kD-phagocyte oxidase p22-phox
CYBB X-linked chronic granulomatous disease (CGD) 91kD-phagocyte oxidase p91-phox
DOCK8 DOCK8 deficiency dedicator of cytokinesis 8 DOCK8
FADD FADD deficiency FAS-associating protein with death domain FADD
FAS ALPS-FAS FAS antigen FAS; CD95
FASLG ALPS-FASLG FAS ligand; CD95 ligand; FASLG
FOXP3 IPEX, immune dysregulation, polyendocrinopathy, enteropathy X-linked forkhead box p3 FOXP3
ICOS ICOS deficiency inducible T-cell costimulator ICOS
ITK lymphoproliferative syndrome type 1 (LPFS1) interleukin 2 inducible T-cell kinase ITK
IFIH1 Aicardi-Goutieres syndrome 7 interferon-induced helicase domain-containing protein 1 IFIH1
IL10 IL-10 deficiency interleukin-10 IL-10
IL10RA IL-10Rα deficiency interleukin-10 receptor alpha IL-10R1
IL10RB IL-10Rβ deficiency interleukin-10 receptor beta IL-10R2
IL21 IL-21 deficiency IL-21 deficiency IL-21
IL21R IL-21R deficiency interleukin-21 receptor IL-21R
IL2RA CD25 deficiency CD25 CD25
ITCH ITCH deficiency ITCHY E3 ubiquitin protein ligase ITCH
LRBA LRBA deficiency lipopolysaccharide responsive beige-like anchor protein LRBA
LYST Chediak-Higashi syndrome lysosomal trafficking regulator LYST
MAGT1 X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN) magnesium transporter 1 MAGT1
NCF2 Autosomal recessive CGD 67kD-phagocyte oxidase p67-phox
NCF4 Autosomal recessive CGD 40kD-phagocyte oxidase p40-phox
NFAT5 NFAT5 haploinsufficiency tonicity-responsive enhancer-binding protein TONEBP
NFKB2 NFKB2 deficiency NF-kappa-B, subunit 2 NFKB2
NFKBIA Anhidrotic ectodermal dysplasia with T-cell immunodeficiency (EDA-ID), IKBA gain I-kappa-B-alpha IKBA
ORAI1 ORAI-I deficiency calcium release-activated calcium modulator 1 ORAI1
PIK3CD Activated PI3K-δ p110-delta protein p110-delta
PIK3R1 PI3KR1 deficiency, PI3KR1 loss of function p85-alpha protein p85-alpha
PLCG2 PLAID (PLCγ2 associated antibody deficiency and immune dysregulation), Familial cold autoinflammatory syndrome 3, APLAID (autoinflammation and PLCγ2 associated antibody deficiency and immune dysregulation) phospholipase C gamma 2 PLCG2
PNP Purine nucleoside phosphorylase (PNP) deficiency purine nucleoside phosphorylase PNP
PRF1 Perforin deficiency (FHL2) perforin perforin
PRKCD PRKC delta deficiency protein kinase C delta PRKCD
RAB27A Griscelli syndrome, type 2 ras-associated protein RAB27A RAB27A
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
RMRP Cartilage hair hypoplasia Mitochondrial RNA-processing endoribonuclease (RNase MRP) RNA RNase MRP (RNA)
RNASEH2A RNASEH2A deficiency, Aicardi-Goutieres syndrome 4 ribonuclease H2 subunit A RNASEH2A
RNASEH2B RNASEH2B deficiency, Aicardi-Goutieres syndrome 2 ribonuclease H2 subunit B RNASEH2B
RNASEH2C RNASEH2C deficiency, Aicardi-Goutieres syndrome 3 ribonuclease H2 subunit C RNASEH2C
SAMHD1 SAMHD1 deficiency, Aicardi-Goutieres syndrome 5 SAM domain and HD domain containing protein 1 SAMHD1
SH2D1A SH2D1A deficiency (XLP1) SH2 domain protein 1A SH2D1A
SLC7A7 lysinuric protein intolerance cationic amino acid transporter 1 SLC7A7
STAT1 STAT1 deficiency signal transducer and activator of transcription 1 STAT1
STAT3 AD-HIES (Job or Buckley Syndrome), STAT3 GOF mutations signal transducer and activator of transcription 3 STAT3
STAT5B STAT5b deficiency signal transducer and activator of transcription 5b STAT5B
STIM1 STIM1 deficiency stromal interaction molecule 1 STIM1
STX11 Syntaxin 11 deficiency, (FHL4) syntaxin 11 STX11
STXBP2 STXBP2 / Munc18-2 deficiency (FHL5) munc18-2 MUNC18-2
TBX1 DiGeorge T-box 1 TBX1
TMEM173 STING–associated vasculopathy, infantile onset stimulator of interferon genes STING
TNFRSF13B TACI deficiency transmembrane activator and CAML interactor TACI
TNFRSF13C BAFF receptor deficiency BAFF receptor BAFFR
TNFRSF12 TWEAK deficiency TNF-related weak inducer of apoptosis TWEAK
TPP2 Tripeptidyl-Peptidase II Deficiency tripeptidyl peptidase II TPP2
TREX1 TREX1 deficiency, Aicardi-Goutieres 3-prime repair exonuclease 1 TREX1
UNC13D UNC13D / Munc13-4 deficiency (FHL3) munc13-4 MUNC13-4
UNG UNG deficiency uracil-DNA glycosylase UNG
WAS Wiskott-Aldrich syndrome, X-linked neutropenia/ myelodysplasia WAS protein WASP
XIAP XIAP deficiency (XLP2) baculoviral IAP-repeat containing protein 4 BIRC4

Monogenic autoimmune disorders are caused by defects in the adaptive or acquired immune response that result in loss of self tolerance. Autoimmunity due to monogenic defects tend to have an earlier age of onset and be more severe than autoimmunity due to complex genetic causes. Depending on the underlying disorder, autoimmunity may be the presenting sign or could appear later in the disease course. Patients with monogenic autoimmunity may have several different autoimmune disorders. These disorders may include autoimmune hemolytic anemia, autoimmune cytopenias, immune thrombocytopenia, juvenile rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, and vasculitis, among others. These patients are also at increased risk for lymphoproliferation.

The clinical sensitivity for this test is unknown. Monogenic autoimmunity is clinically and genetically heterogeneous, and the percentage of patients with autoimmunity and a pathogenic variant(s) in one of the genes offered in this panel has not been determined.

Monogenic autoimmunity can be inherited in several patterns, including autosomal dominant, autosomal recessive, X-linked.

The prevalence of autoimmunity due to monogenic disorders is unknown.

This test may be appropriate for for patients with:

  • early onset autoimmune disease
  • multiple autoimmune phenotypes
  • isolated autoimmunity
  • autoimmunity that is part of a syndrome with non-autoimmune features

  1. Plander, M, Kalman, B. Rare autoimmune disorders with Mendelian inheritance. Autoimmunity. 2016; 49(5):285-97. PMID: 27207228
  2. Patuzzo, G, et al. Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimmun Rev. 2016; 15(9):877-82. PMID: 27392505
  3. Crow, YJ. Type I interferonopathies: a novel set of inborn errors of immunity. Ann. N. Y. Acad. Sci. 2011; 1238:91-8. PMID: 22129056
  4. Rodero, MP, Crow, YJ. Type I interferon-mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview. J. Exp. Med. 2016; 213(12):2527-2538. PMID: 27821552
  5. Lucas, CL, Lenardo, MJ. Identifying genetic determinants of autoimmunity and immune dysregulation. Curr. Opin. Immunol. 2015; 37:28-33. PMID: 26433354
  6. Saifi, M, Wysocki, CA. Autoimmune Disease in Primary Immunodeficiency: At the Crossroads of Anti-Infective Immunity and Self-Tolerance. Immunol Allergy Clin North Am. 2015; 35(4):731-52. PMID: 26454316
  7. Melki, I, Crow, YJ. Novel monogenic diseases causing human autoimmunity. Curr. Opin. Immunol. 2015; 37:1-5. PMID: 26262888
  8. Pathak, S, et al. Autoinflammatory diseases: update on classification diagnosis and management. J. Clin. Pathol. 2017; 70(1):1-8. PMID: 27646526
  9. Picard, C, et al. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J. Clin. Immunol. 2015; 35(8):696-726. PMID: 26482257
  10. Ciccarelli, F, et al. An update on autoinflammatory diseases. Curr. Med. Chem. 2014; 21(3):261-9. PMID: 24164192
  11. Arakelyan, A, et al. Autoimmunity and autoinflammation: A systems view on signaling pathway dysregulation profiles. PLoS ONE. 2017; 12(11):e0187572. PMID: 29099860

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
ACP5 NM_001111035.2
ADA NM_000022.2
ADA2 NM_001282225.1
ADAM17 NM_003183.5
ADAR NM_001111.4
AICDA NM_020661.2
AIRE NM_000383.3
AP3B1 NM_003664.4
BLOC1S6 NM_012388.3
BTK NM_000061.2
CARD14 NM_024110.4
CASP10 NM_032977.3
CASP8 NM_001228.4
CD27 NM_001242.4
CD3G NM_000073.2
CD40LG NM_000074.2
COPA NM_004371.3
CR2 NM_001006658.2
CTLA4 NM_005214.4
CYBA NM_000101.3
CYBB NM_000397.3
DCLRE1C NM_001033855.2
DKC1 NM_001363.4
DOCK8 NM_203447.3
ELANE NM_001972.2
FADD NM_003824.3
FAS NM_000043.5
FASLG NM_000639.2
FOXP3 NM_014009.3
G6PC3 NM_138387.3
ICOS NM_012092.3
IFIH1 NM_022168.3
IL10 NM_000572.2
IL10RA NM_001558.3
IL10RB NM_000628.4
IL1RN NM_173841.2
IL21 NM_021803.3
IL21R NM_021798.3
IL2RA NM_000417.2
IL2RG NM_000206.2
IL36RN NM_012275.2
ITCH NM_031483.6
ITGB2 NM_000211.4
ITK NM_005546.3
LIG4 NM_002312.3
LPIN2 NM_014646.2
LRBA NM_006726.4
LYST NM_000081.3
MAGT1 NM_032121.5
MEFV NM_000243.2
MVK NM_000431.3
NCF2 NM_000433.3
NCF4 NM_013416.3
NFAT5 NM_138714.3
NFKB2 NM_001077494.3
NFKBIA NM_020529.2
NLRC4 NM_021209.4
NLRP12 NM_144687.3
NLRP3 NM_004895.4
NOD2 NM_022162.2
ORAI1 NM_032790.3
PIK3CD NM_005026.3
PIK3R1 NM_181523.2
PLCG2 NM_002661.4
PNP NM_000270.3
PRF1 NM_001083116.1
PRKCD NM_006254.3
PSMB8 NM_148919.3
PSTPIP1 NM_003978.3
RAB27A NM_004580.4
RAC2 NM_002872.4
RAG1 NM_000448.2
RAG2 NM_000536.3
RBCK1 NM_031229.3
RFX5 NM_000449.3
RFXANK NM_003721.3
RFXAP NM_000538.3
RMRP NR_003051.3
RNASEH2A NM_006397.2
RNASEH2B NM_024570.3
RNASEH2C NM_032193.3
RTEL1 NM_001283009.1
SAMHD1 NM_015474.3
SH2D1A NM_002351.4
SH3BP2 NM_003023.4
SLC29A3 NM_018344.5
SLC37A4 NM_001164277.1
SLC7A7 NM_001126106.2
STAT1 NM_007315.3
STAT3 NM_139276.2
STAT5B NM_012448.3
STIM1 NM_003156.3
STX11 NM_003764.3
STXBP2 NM_006949.3
TBX1 NM_080647.1
TMEM173 NM_198282.3
TNFRSF13B NM_012452.2
TNFRSF13C NM_052945.3
TNFRSF1A NM_001065.3
TNFSF12 NM_003809.2
TPP2 NM_003291.2
TREX1 NM_033629.4
TRNT1 NM_182916.2
TTC7A NM_020458.3
UNC13D NM_199242.2
UNG NM_080911.2
WAS NM_000377.2
XIAP NM_001167.3
ZAP70 NM_001079.3