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Coffin-Siris Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10221 ARID1A 81479,81479 Order Options and Pricing
ARID1B 81479,81479
ARID2 81479,81479
DPF2 81479,81479
PHF6 81479,81479
SMARCA2 81479,81479
SMARCA4 81479,81479
SMARCB1 81479,81479
SMARCC2 81479,81479
SMARCE1 81479,81479
SOX11 81479,81479
SOX4 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10221Genes x (12)81479 81479(x24) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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 backbone).

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

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Coffin-Siris syndrome (CSS) is a multi-systemic genetic disease characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, variable developmental or cognitive delay/intellectual disability, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Other variable findings include short stature, feeding difficulties, ophthalmologic abnormalities, cardiac anomalies and hearing loss (Schrier Vergano et al. 2021. PubMed ID: 23556151; Vergano and Deardorff. 2014. PubMed ID: 25169447).

To date, ~ 200 cases of molecularly confirmed CSS have been reported. The exact prevalence and incidence is not clear, but this disorder is probably underestimated as not all individuals may have come to medical attention. Molecular genetic testing is particularly useful to reach an accurate diagnosis (Schrier Vergano et al. 2021. PubMed ID: 23556151).

Genetics

The majority of CSS is inherited in an autosomal dominant (AD) manner with high penetrance. Most patients reported to date have a de novo pathogenic variant. Pathogenic variants or genomic rearrangements in the following genes have been reported to be causative for CSS and other CSS-like conditions: ARID1A, ARID1B, ARID2, DPF2, PHF6, SMARCA2SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX4, and SOX11 (Santen et al. 2013. PubMed ID: 23929686; Kosho et al. 2014. PubMed ID: 25169878; Hempel et al. 2016. PubMed ID: 26543203; Vasileiou et al. 2018. PubMed ID: 29429572; Schrier Vergano et al. 2021. PubMed ID: 23556151). Most of these genes encode for subunit proteins of BAF complex, also known as the SWI/SNF complex, which is essential in chromatin remodeling (Watanabe et al. 2014. PubMed ID: 24788099; Vasko et al. 2021. PubMed ID: 34205270). Genotype-phenotype correlations have been observed in clinically diagnosed individuals with confirmed pathogenic variants in the above-mentioned genes (Schrier Vergano et al. 2021. PubMed ID: 23556151; Vasko et al. 2021. PubMed ID: 34205270).

Pathogenic variants in ARID1B are the most common cause of CSS, followed by variants in SMARCA4 (Wieczorek et al. 2013. PubMed ID: 23906836; Schrier Vergano et al. 2021. PubMed ID: 23556151; Vasko et al. 2021. PubMed ID: 34205270). Pathogenic variants in these genes include single nucleotide changes, small insertions/duplications, single or multiple exon deletions, as well as entire gene deletions (Human Gene Mutation Database). Pathogenic variants in SOX11 have also been reported to cause CSS. SOX11 is a transcription factor downstream of the BAF complex and plays an important role in neurogenesis during brain development (Tsurusaki et al. 2014. PubMed ID: 24886874; Hempel et al. 2016. PubMed ID: 26543203). Additionally, de novo missense variants in SOX4, another member of the family of SOX transcription factors, have been reported in individuals with clinical characteristics similar to CSS (Zawerton et al. 2019. PubMed ID: 30661772). 

Heterozygous pathogenic variants in SMARCA4 and SMARCB1 have also been reported to cause the rhabdoid tumor predisposition syndrome (Roberts and Biegel. 2009. PubMed ID: 19305156; Hasselblatt et al. 2011. PubMed ID: 21566516; Biegel et al. 2014. PubMed ID: 25169151). Heterozygous pathogenic variants in SMARCB1 cause schwannomatosis, a condition characterized by multiple cutaneous neurilemmomas and spinal schwannomas (Merker et al. 2012. PubMed ID: 22927469). Kidney malformations are more common in individuals with SMARCB1 and SMARCE1 variants (Vasko et al. 2021. PubMed ID: 34205270).

Pathogenic variants in PHF6 are mainly associated with X-linked Börjeson–Forssman–Lehmann syndrome, which is characterized by mild to moderately impaired intellectual disability, seizures, hypotonia, hypogonadism, obesity with marked gynecomastia, tapering fingers, and large, but not deformed, ears (Lower et al. 2002. PubMed ID: 12415272; Wieczorek et al. 2013. PubMed ID: 23906836; Schrier Vergano et al. 2021. PubMed ID: 23556151). In addition, relatively few cases have been reported to be associated with single exon or partial gene deletion involving the X-linked PHF6 gene (Di Donato et al. 2014. PubMed ID: 24380767; Zweier et al. 2013. PubMed ID: 24092917), and heterozygous missense or splicing variants in DPF2 (Vasileiou et al. 2018. PubMed ID: 29429572). 

Variants in SMARCA2 are mainly reported in patients with autosomal dominant Nicolaides-Baraitser syndrome characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability, and most of these variants are de novo missense (Van Houdt et al. 2012. PubMed ID: 22366787).

See individual gene summaries for information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

This test is expected to detect causative variants in about 60% of patients with Coffin-Siris syndrome (Schrier Vergano et al. 2021. PubMed ID: 23556151).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 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

Individuals with symptoms consistent with Coffin-Siris syndrome are candidates for this test.

Genes

Official Gene Symbol OMIM ID
ARID1A 603024
ARID1B 614556
ARID2 609539
DPF2 601671
PHF6 300414
SMARCA2 600014
SMARCA4 603254
SMARCB1 601607
SMARCC2 601734
SMARCE1 603111
SOX11 600898
SOX4 184430
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

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Citations

  • Biegel et al. 2014. PubMed ID: 25169151
  • Di Donato et al. 2014. PubMed ID: 24380767
  • Hasselblatt et al. 2011. PubMed ID: 21566516
  • Hempel et al. 2016. PubMed ID: 26543203
  • Human Gene Mutation Database (Bio-base).
  • Kosho et al. 2014. PubMed ID: 25169878
  • Lower et al. 2002. PubMed ID: 12415272
  • Merker et al. 2012. PubMed ID: 22927469
  • Roberts and Biegel. 2009. PubMed ID: 19305156
  • Santen et al. 2013. PubMed ID: 23929686
  • Schrier Vergano et al. 2021. PubMed ID: 23556151
  • Tsurusaki et al. 2014. PubMed ID: 24886874
  • Van Houdt et al. 2012. PubMed ID: 22366787
  • Vasileiou et al. 2018. PubMed ID: 29429572
  • Vasko et al. 2021. PubMed ID: 34205270
  • Vergano and Deardorff. 2014. PubMed ID: 25169447
  • Watanabe et al. 2014. PubMed ID: 24788099
  • Wieczorek et al. 2013. PubMed ID: 23906836
  • Zawerton et al. 2019. PubMed ID: 30661772
  • Zweier et al. 2013. PubMed ID: 24092917

Ordering/Specimens

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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