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  • Test code: 04151
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae RASopathies and Noonan Spectrum Disorders Panel

Test description

The Invitae RASopathies and Noonan Spectrum Disorders Panel analyzes genes that belong to the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway, which is associated with a class of pediatric conditions termed “RASopathies” (also known as Noonan Spectrum Disorders). RASopathies are characterized by short stature, distinctive facial features, heart defects, developmental delay, and an increased risk of malignancies. These genes were selected based on the available evidence to date to provide a broad analysis for inherited RASopathies and related conditions. The genetic heterogeneity associated with these conditions can make it difficult to use phenotype as the sole criterion to select a definitive cause. Broad panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

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Primary panel (28 genes)

A2ML1 ACTB ACTG1 BRAF CBL HRAS KAT6B KRAS LZTR1 MAP2K1 MAP2K2 MRAS NF1 NRAS NSUN2 PPP1CB PTPN11 RAF1 RASA1 RASA2 RIT1 RRAS RRAS2 SHOC2 SOS1 SOS2 SPRED1 YWHAZ

  • RASopathies (including Noonan syndrome, Noonan syndrome with multiple lentigines, cardio-facio-cutaneous syndrome, and Costello syndrome; for these subtypes, see detailed descriptions below)
  • Noonan syndrome with multiple lentigines (NSML)
  • Cardio-facio-cutaneous (CFC) syndrome
  • Costello syndrome
  • Baraitser-Winter syndrome
  • Capillary malformation-arteriovenous malformation (CM-AVM)
  • Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and genitopatellar syndrome (GPS)
  • Legius syndrome
  • NF1-related conditions

To view the complete clinical description of this panel, click here.

RASopathies can occur in both autosomal dominant and autosomal recessive inheritance patterns.

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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
A2ML1 NM_144670.4
ACTB NM_001101.3
ACTG1 NM_001614.3
BRAF NM_004333.4
CBL NM_005188.3
HRAS NM_005343.2
KAT6B NM_012330.3
KRAS NM_004985.4
LZTR1 NM_006767.3
MAP2K1 NM_002755.3
MAP2K2 NM_030662.3
MRAS NM_012219.4
NF1* NM_000267.3
NRAS NM_002524.4
NSUN2* NM_017755.5
PPP1CB NM_206876.1
PTPN11 NM_002834.3
RAF1 NM_002880.3
RASA1 NM_002890.2
RASA2 NM_006506.3
RIT1 NM_006912.5
RRAS NM_006270.4
RRAS2 NM_012250.5
SHOC2 NM_007373.3
SOS1 NM_005633.3
SOS2 NM_006939.2
SPRED1 NM_152594.2
YWHAZ NM_001135699.1

NF1: Sequencing analysis for exons 2, 7, 25, 41, 48 includes only cds +/- 10 bp.
NSUN2: Deletion/duplication analysis is not offered for exon 9.