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Autism Spectrum Disorders/Intellectual Disability via the ASH1L 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
ASH1L 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
5249ASH1L81479 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.

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

Autism Spectrum Disorders (ASD) include several neurodevelopmental disorders characterized by varying degrees of social impairment, communication ability, and propensity for restricted interests and repetitive behavior(s) (Levy et al. 2009). ASD usually presents by age 3. Diagnosis is based on the degree and severity of symptoms and behaviors (Diagnostic and Statistical Manual of Mental Disorders (DSM-5); McPartland et al. 2016). Comorbidities occur in more than 70% of cases and include intellectual disability (ID), epilepsy, language deficits, and gastrointestinal problems (Sztainberg and Zoghbi 2016). Recent studies using whole exome trio studies have identified novel gene candidates, with familial and de novo variants from several hundred genes now implicated in the development of ASD (Bourgeron 2016).


Genetic aberrations are reported to be responsible for 50%-90% and 15%-50% of ASD and ID cases, respectively, and inheritance overall is multifactorial (Larsen et al. 2016; Karam et al. 2015). Incidence of ASD is approximately 1 in 68 individuals with a male-to-female ratio of 4:1 (Center for Disease Control 2014). De novo missense and likely gene disrupting variants are 15% and 75% more frequent in ASD patients than unaffected controls, respectively (Iossifov et al. 2014).

ASH1L (absent, small, or homeotic 1-like homolog, also known as KMT2H) is a histone lysine methyltransferase that occupies and modifies promoter region chromatin to influence gene regulation and development through H3K36me2 methylation. ASH1L protein levels are enriched in the hippocampus; however ASH1L’s role(s) in the brain are still poorly understood (Zhu et al. 2016). ASH1L has been shown to mediate activity-dependent repression of NRXN1, which encodes the synaptic cell adhesion molecule neurexin 1. Activity-dependent synapse elimination is believed to refine neuronal wiring during the late stages of postnatal development. Mice homozygous for disrupting variants in ASH1L are apparently not viable, while heterozygous mice do not show any abnormalities of the brain (Zhu et al. 2016).

ASH1L pathogenic variants result in ASD/ID symptoms in an autosomal dominant manner, as all affected individuals reported to date are heterozygous and several de novo variants have been implicated with disease development. The human ASH1L gene contains 27 protein-coding exons which encode a 2,964 amino acid protein. ASH1L contains a SET domain, four AT hooks, bromodomain, bromo-adjacent homology domain, PHD finger, and a MYND ligand domain (Gregory et al. 2007). At least 1 nonsense and 3 missense (two de novo) variants have been reported in individuals presenting with intellectual disability (100%), ASD (25%), facial dysmorphism (50%), abnormal behavior (75%), gastrointestinal problems (50%), eye anomalies (50%), myelination delay (1 case), and skeletal abnormalities (50%) (Okamoto et al. 2017). The nonsense variant occurred before the multidomain region of ASH1L and only one missense variant has been reported in the bromo-adjacent homology domain (most C-terminal domain) (Okamoto et al. 2017).

Clinical Sensitivity - Sequencing with CNV PGxome

Currently, the contribution of de novo and inherited factors to ASD risk is estimated to be approximately 50-60% (Krumm et al. 2015). ASH1L is categorized as a gene with ‘high confidence’ regarding its susceptibility for ASD in the Simons Foundation Autism Research Initiative (SFARI) Database (https://gene.sfari.org/GeneDetail/ASH1L). However, more than 700 genes have been associated with ASD features (Bourgeron 2016). Based on recent large whole exome sequencing studies, causative variants in ASH1L were identified in approximately 1/1000 individuals within multiple ASD and ID cohorts (De Rubeis et al. 2014; Grozeva et al. 2015; Wang et al. 2016). However, one study focused specifically on an ID cohort identified 7/765 individuals with missense variants in ASH1L (de Ligt et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the ASH1L 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).

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

The majority of missense and nonsense variants reported in ASH1L are de novo in nature. However, individuals with family members having known ASH1L variants and/or presenting with ID and/or ASD, facial dysmorphism, skeletal anomalies, growth failure, myelination delay, orofacial hypotonia and horizontal nystagmus are good candidates for this test.


Official Gene Symbol OMIM ID
ASH1L 607999
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Mental Retardation, Autosomal Dominant 52 AD 617796


  • Bourgeron T. 2016. Comptes Rendus Biologies. 339: 300-7. PubMed ID: 27289453
  • Center for Disease Control and Prevention. 2014. Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C. : 2002). 63: 1-21. PubMed ID: 24670961
  • de Ligt J. et al. 2012. New England Journal of Medicine 367: 1921-1929. PubMed ID: 23033978
  • De Rubeis S. et al. 2014. Nature. 515: 209-15. PubMed ID: 25363760
  • Gregory G.D. et al. 2007. Molecular and Cellular Biology. 27: 8466-79. PubMed ID: 17923682
  • Grozeva D. et al. 2015. Human Mutation. 36: 1197-204. PubMed ID: 26350204
  • Iossifov I. et al. 2014. Nature. 515: 216-21. PubMed ID: 25363768
  • Karam S.M. et al. 2015. American Journal of Medical Genetics. Part A. 167: 1204-14. PubMed ID: 25728503
  • Krumm N. et al. 2015. Nature Genetics. 47: 582-8. PubMed ID: 25961944
  • Larsen E. et al. 2016. Molecular Autism. 7: 44 PubMed ID: 27790361
  • Levy S.E. et al. 2009. Lancet. 374: 1627-38. PubMed ID: 19819542
  • McPartland J.C. et al. 2016. Encyclopedia of Mental Health. 2: 124-130.
  • Okamoto N. et al. 2017. American Journal of Medical Genetics. Part A. Epub Ahead of Print. PubMed ID: 28394464
  • Sztainberg Y., Zoghbi H.Y. 2016. Nature Neuroscience. 19: 1408-17. PubMed ID: 27786181
  • Wang et al. 2016. PubMed ID: 27824329
  • Zhu T. et al. 2016. Scientific Reports. 6: 26597. PubMed ID: 27229316


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