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.
Genes tested
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
Order test
Primary panel (28 genes)
Customized gene selection (0 included, 0 excluded)
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
Clinical information
Disorders tested
- 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
Clinical description
To view the complete clinical description of this panel, click here.
Inheritance
RASopathies can occur in both autosomal dominant and autosomal recessive inheritance patterns.
Assay
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.
