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Phelan-Mcdermid Syndrome, 22q13 Deletion Syndrome, or Autism Spectrum Disorder via the SHANK3 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
SHANK3 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9841SHANK381479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Phelan-McDermid syndrome is a rare form of intellectual disability. 84% of patients with Phelan-McDermid syndrome meet the criteria for Autism Spectrum Disorder (Betancur and Buxbaum 2013). Major features of Phelan-McDermid syndrome include neonatal hypotonia, global developmental delay, moderate to severe intellectual disability, gait disturbance, increased tolerance to pain, absent or severely delayed speech, and autistic-like behavior with reduced social interaction and poor eye contact (Phelan and McDermid 2012). Notably, overall growth is normal. Dysmorphic features commonly displayed by patients include flat midface with a wide brow, long eyelashes, bulbous nose, sacral dimple, dysplastic ears, toenails and large hands. Brain MRI commonly reveals abnormalities including thinning of the corpus callosum, white matter changes and ventricular dilation (Soorya et al. 2013).


Phelan-McDermid syndrome is inherited in an autosomal dominant manner and is caused by either deletion of 22q13.33 or SHANK3 pathogenic variants. SHANK3 is contained within reported 22q13 deletion intervals and is believed to account for the core features of Phelan-Mcdermid syndrome. The causative pathogenic variants include missense and nonsense variants, splicing variants, small deletions and insertions, large deletions encompassing the SHANK3 gene, as well as chromosomal re-arrangements. About ~80% of SHANK3 chromosomal abnormalities are interstitial or terminal q22 deletions. Most cases of Phelan-McDermid syndrome are sporadic resulting from de novo pathogenic variants in the SHANK3 locus.

SHANK3 encodes a scaffold protein that is primarily expressed in the brain, particularly in the cerebral cortex and cerebellum. The SHANK3 protein localizes to the core of postsynaptic glutamatergic synapses. SHANK3 contains multiple protein binding domains which allow it to interact and organize a series of other proteins. SHANK3 also interacts with neuroligins in the postsynatpic membrane, which is required for proper synapse formation (Phelan and McDermid 2012; Cochoy et al 2015).

Clinical Sensitivity - Sequencing with CNV PGxome

The majority of reported pathogenic variants in SHANK3 are large deletions (Human Gene Mutation Database), therefore the clinical sensitivity of SHANK3 sequencing with CNV detection is expected to be significantly higher than a sequencing only test.

Reported 22q13 deletions range in size from 100kb to 4Mb. In a recent study of Phelan-McDermid syndrome patients, ~72% (30/44) had simple 22q13 terminal deletions, 14% had deletions that resulted in the formation of ring chromosomes, 9% had interstitial deletions which included SHANK3 and 7% contained unbalanced translocations (Bonaglia et al. 2011). Balanced translocations in which the breakpoint disrupts SHANK3 have been reported, but their frequency is unknown.

Testing Strategy

This test provides full coverage of all coding exons of the SHANK3 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Exon 11 of SHANK3 is not sequenced due to DNA structural difficulties and inconsistency in the reference sequence. No pathogenic variants have been reported in this exon.

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

SHANK3 sequencing is recommended for patients suspected to have Phelan-McDermid syndrome, or Autism Spectrum Disorder, atypical Prader-Willi syndrome and Angelman syndrome.


Official Gene Symbol OMIM ID
SHANK3 606230
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Phelan-Mcdermid Syndrome AD 606232


  • Betancur C., Buxbaum JD. 2013. Molecular autism. 4: 17. PubMed ID: 23758743
  • Bonaglia MC. et al. 2011. PLoS genetics. 7: e1002173. PubMed ID: 21779178
  • Cochoy DM. et al. 2015. Molecular autism. 6: 23. PubMed ID: 26045941
  • Human Gene Mutation Database (Bio-base).
  • Phelan K., McDermid HE. 2012. Molecular syndromology. 2: 186-201. PubMed ID: 22670140
  • Soorya L. et al. 2013. Molecular autism. 4: 18. PubMed ID: 23758760


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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View Ordering Instructions

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2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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