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Test ID: PMNSR Postmortem Noonan and Related Panel, Varies

Advisory Information

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 mutation testing) is available for the genes on this panel. See:

-KVAR1 / Known Variant Analysis-1 Variant, Varies

-KVAR2 / Known Variant Analysis-2 Variants, Varies

-KVAR3 / Known Variant Analysis-3+ Variants, Varies


Call 800-533-1710 to confirm the appropriate test for targeted testing.

Necessary Information

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.

Specimen Required


Specimen Type: Tissue

Container/Tube: Tissue block

Collection Instructions: 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.

Specimen Stability Information: Ambient



Specimen Type: Blood spot

Container/Tube: Whatman FTA Classic Card or Whatman Protein Saver 903 Card

Specimen Volume: 3-5 blood spots

Collection Instructions:

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.

Specimen Stability Information: Ambient (preferred)/Refrigerated


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send a Cardiovascular Test Request (T724) with the specimen.

Useful For

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

Method Name

Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Supplemental Sanger Sequencing

Reporting Name

Postmortem Noonan and Related Panel

Specimen Type


Specimen Minimum Volume

Tissue: See Specimen Required
Blood Spots: 3

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)

Clinical Information

Noonan syndrome (NS) is an autosomal dominant disorder of variable expressivity whose characteristic features can include short stature, congenital heart defects, characteristic facial dysmorphology, unusual chest shape, developmental delay of varying degree, cryptorchidism, and coagulation defects, among other features. In approximately 20% to 30% of cases, Noonan syndrome and related disorders are associated with hypertrophic cardiomyopathy, which may lead to sudden cardiac death. Postmortem diagnosis of Noonan syndrome or a related disorder may assist in confirmation of the cause of death, as well as risk assessment in living family members. Other heart defects associated with Noonan syndrome and related disorders include pulmonary valve stenosis (20%-50%), atrial septal defects (6%-10%), ventricular septal defects (approximately 5%), and patent ductus arteriosus (approximately 3%). Facial features, which tend to change with age, may include hypertelorism, downward-slanting eyes, epicanthal folds, and low-set and posteriorly rotated ears. Mild mental retardation is seen in up to one-third of adults. 


The incidence of NS is estimated to be between 1 in 1,000 and 1 in 2,500, although subtle expression in adulthood may cause this number to be an underestimate. NS is genetically heterogeneous, with 4 genes currently associated with the majority of cases: PTPN11, RAF1, SOS1, and KRAS. Heterozygous variants in NRAS, HRAS, BRAF, SHOC2, MAP2K1, MAP2K2, and CBL have also been associated with a smaller percentage of NS and related phenotypes. All of these genes are involved in a common signal transduction pathway known as the Ras-mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway is important for cell growth, differentiation, senescence, and death. Molecular genetic testing of all of the known genes identifies a pathogenic variant in approximately 75% of affected individuals. NS can be sporadic and due to new (de novo) variants; however, an affected parent can be recognized in 30% to 75% of families.


Some studies have shown that there is a genotype-phenotype correlation associated with NS. An analysis of a large cohort of individuals with NS has suggested that PTPN11 variants are more likely to be found when pulmonary stenosis is present, while hypertrophic cardiomyopathy is commonly associated with RAF1 variants, but rarely associated with PTPN11.


A number of related disorders exist that have phenotypic overlap with NS and are caused by variants in the same group of genes. PTPN11 and RAF1 variants have been associated with LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and deafness) syndrome, an autosomal dominant disorder sharing several clinical features with NS. Variants in BRAF, MAP2K1, MAP2K2, and KRAS have been identified in individuals with cardiofaciocutaneous (CFC) syndrome, a condition involving congenital heart defects, cutaneous abnormalities, Noonan-like facial features, and severe psychomotor developmental delay. Costello syndrome, which is characterized by coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, failure to thrive, cardiac anomalies, and developmental disability has been primarily associated with variants in HRAS. Variation in SHOC2 has been associated with a distinctive phenotype involving features of Noonan syndrome and loose anagen hair.


Genes included in the Postmortem Noonan and Related Panel




Disease Association


V-RAF murine sarcoma viral oncogene homolog b1


Noonan/CFC/Costello syndrome


CAS-BR-M murine ecotropic retroviral transforming sequence homolog


Noonan-like syndrome disorder


V-HA-RAS Harvey rat sarcoma viral oncogene homolog


Costello syndrome


V-KI-RAS Kirsten rat sarcoma viral oncogene homolog


Noonan/CFC/Costello syndrome


Mitogen-activated protein kinase, kinase 1




Mitogen-activated protein kinase, kinase 2




Neuroblastoma ras viral oncogene homolog


Noonan syndrome


Protein-tyrosine phosphatase, nonreceptor-type, 11


Noonan/CFC/LEOPARD syndrome


V-raf-1 murine leukemia viral oncogene homolog 1


Noonan/LEOPARD syndrome


Suppressor of clear, c. Elegans, homolog of


Noonan-syndrome like with loose anagen hair


Son of sevenless, drosophila, homolog 1


Noonan- like syndrome with loose anagen hair

Abbreviations: autosomal dominant (AD)

Reference Values

An interpretive report will be provided.


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.

Clinical Reference

1. Online Mendelian Inheritance in Man. Accessed 10/5/2017. Available at

2. Tartaglia M, Gelb BD, Zenker M: Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab 2011;25(1):161-179

3. Rauen KA: Cardiofaciocutaneous Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle. 1993-2018. 2007 Jan 18 (Updated 2016 Mar 3). Accessed 2/2018. Available at

4. Allanson JE, Roberts AE: Noonan Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington. Seattle. 1993-2018. 2001 Nov 15 (Updated 2016 Feb 25). Accessed 2/2018. Available at

5. Gripp KW, Lin AE: Costello Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle. 1993-2018. 2006 Aug 29 (Updated 2012 Jan 12). Accessed 2/2018. Available at

6. Gelb BD, Tartaglia M: Noonan Syndrome with Multiple Lentigines. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle. 1993-2018. 2007 Nov 30 (Updated 2015 May 14) Accessed 2/2018. Available at

Day(s) and Time(s) Performed

Wednesday; Varies

Analytic Time

6 weeks

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information




81405 X2

81406 X6

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PMNSR Postmortem Noonan and Related Panel In Process


Result ID Test Result Name Result LOINC Value
BA1423 Gene(s) Evaluated 36908-2
BA1424 Result Summary 50397-9
BA1425 Result Details 82939-0
BA1426 Interpretation 69047-9
BA1427 Additional Information 48767-8
BA1428 Method 49549-9
BA1429 Disclaimer 62364-5
BA1430 Reviewed by 18771-6
Mayo Clinic Laboratories | Cardiology Catalog Additional Information:

multi-gene panel