BRAF, Cardiofaciocutaneous (CFC), CBL, Costello Syndrome (CS), HRAS, KRAS, LEOPARD Syndrome (LS), MAP2K1, MAP2K2, Multiple Lentigines, Next Gen Sequencing Test, Noonan Syndrome (NS), NRAS, PTPN11, RAF1, SHOC2, SOS1, FFPE, Postmortem, Sudden cardiac arrest, Sudden cardiac death, Sudden unexplained death, Sudden death
This test includes next-generation sequencing and supplemental Sanger sequencing to evaluate the BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, SHOC2, and SOS1 genes.
Providing a comprehensive postmortem genetic evaluation in the setting of sudden cardiac death and suspicion for Noonan syndrome or related disorders
Identification of a pathogenic variant in the decedent, which may assist with risk assessment and predictive testing of at-risk family members
This test is intended for use on postmortem samples (eg, formalin-fixed, paraffin-embedded [FFPE] tissue block; dried blood spot) when whole blood is not available.
This test uses next-generation sequencing to test for variants in the BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, SHOC2, and SOS1 genes.
This test may aid in the postmortem diagnosis of Noonan syndrome, LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and deafness) syndrome, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, or a related disorder.
Identification of a pathogenic variant may assist with familial risk assessment, screening, and genetic counseling.
This test is intended for use when EDTA whole blood is not available and formalin-fixed, paraffin-embedded (FFPE) tissue or dried blood spots are the only available samples. If EDTA whole blood is available, order NSRGP / Noonan Syndrome and Related Disorders Multi-Gene Panel, Blood.
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Mutation, Targeted Testing, Varies.
Submit a formalin-fixed, paraffin-embedded tissue block.Additional Information: Testing will be attempted on blocks of any age but may be canceled if adequate DNA concentration cannot be obtained.
1. Completely fill at least 3 circles on the filter paper card
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
1. Noonan Spectrum Gene Testing Patient Information Sheet (T689) is required, see Special Instructions. Testing may proceed without the patient information however it aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to complete the form and send it with the specimen.
2. Pathology report must accompany specimen in order for testing to be performed. Include physician name and phone number with the specimen.
This test is intended for use when EDTA whole blood is not available and formalin-fixed, paraffin-embedded (FFPE) tissue or blood spots are the only available samples. DNA extracted from FFPE tissue can be degraded, which results in a higher failure rate (approximately 5%) for next-generation sequencing when compared to DNA extracted from whole blood. Due to the quality of DNA extracted from FFPE, the acceptable coverage threshold is lower than that of the equivalent blood assays. Coverage of at least 40X is expected for all regions assessed but may be adjusted on a case-by-case basis at the discretion of the laboratory director. Sanger sequencing may be used in regions that do not achieve this rate of coverage at the discretion of laboratory director. Genomic regions that are not sufficiently covered for analysis and interpretation will be indicated on the laboratory report. Sanger sequencing on DNA extracted from FFPE may also result in quality limitations when compared to testing on DNA extracted from blood.
Some individuals who have involvement of 1 or more of the genes on the panel may have a variant that is not identified by the methods used (eg, promoter variants, deep intronic variants). The absence of a variant, therefore, does not eliminate the possibility of Noonan syndrome or a related disorder.
Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
If testing was performed because of a family history of Noonan syndrome or a related disorder, it is often useful to first test an affected family member. Identification of a pathogenic variant in an affected individual would allow for more informative testing of at risk individuals.
Next-generation sequencing may not detect all types of genetic variants. Additionally, rare variants may be present that could lead to false-negative or false-positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes.
For blood spot sample type: If the patient has had an allogeneic blood or marrow transplant or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion these results may be inaccurate due to the presence of donor DNA. Reclassification of Variants Policy:
At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.
Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.
Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.