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  • Test code: 08142
  • 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 Herpes Simplex Encephalitis Panel

Test description

The Invitae Herpes Simplex Encephalitis Panel analyzes up to six genes that are associated with monogenic susceptibility to herpes simplex encephalitis (HSE). 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 (4 genes)
Add-on Predisposition to Multiple Viral Infections Genes (2 genes)

Patients with STAT1 and TYK2 deficiencies have been reported with numerous viral infections including HSE and mycobacterial disease. Given that these patients are also susceptible to HSE, analyzing theses gene may be appropriate. These genes can be added at no additional charge.

STAT1 TYK2



Gene Disorder Protein name Protein symbol
TICAM1 TRIF deficiency TIR-domain containing adaptor inducing interferon beta TRIF
TLR3 TLR3 deficiency Toll-like receptor 3 TLR3
TRAF3 TRAF3 deficiency CD40 binding protein CD40BP
UNC93B1 UNC93B1 deficiency UNC93, C. elegans homolog of B1 UNC93B1

Herpes simplex encephalitis (HSE) occurs in the rare cases in which the herpes simplex virus-1 (HSV-1) invades the central nervous system and causes focal necrotizing infections within the brain. HSV-1 is common in the general population, and is often asymptomatic or associated with a mild presentation (i.e. herpes labialis, or cold sores). Monogenic susceptibility to HSE are due to defects in interferon immunity. These primary immunodeficiencies typically result in susceptibility to HSE in children. Patients with HSE typically present with fever, headache, and an altered level of consciousness. Untreated, HSE is fatal in at least 70% of cases. Fortunately, the mortality and morbidity have been drastically reduced with antiviral therapy. One third to one half of affected individuals suffer life-long neurological sequelae of varying severity. Thirty percent of all HSE cases occur in children under the age of 20 years, with peak age of onset between 3 months and 3 years of age, coinciding with the time of primary infection. There is a second peak of incidence later in life (>50yrs), probably due to viral reactivation from latency.

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

The inheritance pattern of mendelian susceptibility to HSE depends on the underlying genetic etiology:

Gene Inheritance
TICAM1 Autosomal recessive and autosomal dominant
TLR3 Autosomal recessive and autosomal dominant
TRAF3 Autosomal dominant
UNC93B1 Autosomal recessive

HSE is a rare infection of the central nervous system affecting about two to four per 1,000,000 individuals per year. Monogenic susceptibility to HSE accounts for a rare but unknown proportion of these cases.

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
STAT1 NM_007315.3
TICAM1 NM_182919.3
TLR3 NM_003265.2
TRAF3 NM_003300.3
TYK2 NM_003331.4
UNC93B1 NM_030930.3