Summary and Pricing
Test MethodExome Sequencing with CNV Detection
|Test Code||Test Copy Genes||Gene CPT Codes Copy CPT Codes|
|10431||ACVR2B||81479,81479||Order Options and Pricing|
|Test Code||Test Copy Genes||Panel CPT Code||Gene CPT Codes Copy CPT Code||Base Price|
|10431||Genes x (133)||81479||81223(x1), 81404(x1), 81405(x1), 81406(x4), 81407(x3), 81408(x2), 81479(x254)||$1240||Order Options and Pricing|
- Fang Xu, PhD, FACMG
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 PGxome 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).
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.
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
- Fang Xu, PhD, FACMG
Clinical Features and Genetics
Ciliopathies are a group of genetic disorders caused by disruption of the formation or function of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal cystic disease and hepatobiliary disease, situs abnormalities, retinal degeneration, cerebellar anomalies, postaxial polydactyly, bronchiectasis and infertility. See individual disease summaries for information about clinical features and spectra of pathogenic variants.
Joubert syndrome and related disorders (JSRD) are marked by hypotonia, abnormal ocular movements, neonatal respiratory difficulties, intellectual disability, hypoplasia of the cerebellar vermis, and malformation of the brainstem. The brain malformations lead to the "molar tooth sign" on cranial MRI, which is pathognomonic for JSRD. Other variable JSRD features include cystic kidneys, nephronophthisis, retinal dystrophy, ocular coloboma, occipital encephalocele, polydactyly, ataxia, and hepatic fibrosis. For more information, see Parisi and Glass. 2017. PubMed ID: 20301500; Doherty 2009. PubMed ID: 19778711; Parisi et al. 2007. PubMed ID: 17377524; Brancati et al. 2010. PubMed ID: 20615230.
Meckel Gruber Syndrome
Meckel-Gruber syndrome (MKS) is a lethal autosomal recessive condition, also marked by brain malformation, cystic renal disease and polydactyly (Alexiev et al. 2006. PubMed ID: 16879033; Hartill et al. 2017. PubMed ID: 29209597). In MKS, the pathognomonic feature is occipital encephalocele, which is generally identified during routine sonography between 12 and 20 weeks of gestation. MKS is a common cause of prenatal echogenic kidneys (Chaumoitre et al. 2006. PubMed ID: 17094077). Nearly all MKS infants are stillborn or die shortly after birth (Hartill et al. 2017. PubMed ID: 29209597; Parisi and Glass. 2017. PubMed ID: 20301500).
Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder marked by primary features of obesity, polydactyly, pigmentary retinopathy, hypogonadism, renal anomalies and mental retardation (Elbedour et al. 1994. PubMed ID: 7802002; Sheffield 2010. PubMed ID: 20697559). Secondary features include diabetes, hypertension and congenital heart defects (Green et al. 1989. PubMed ID: 2779627). Although BBS is a rare condition, diagnosis is complicated because many of the clinical features (i.e. obesity, diabetes, hypertension and developmental delay) are common. In addition, many BBS clinical features overlap with those of other well-described developmental disorders, including MKS, Joubert syndrome, nephronophthisis, Senior-Loken syndrome and Leber congenital amaurosis. Thus, molecular testing is often useful for confirmation of a clinical diagnosis and to aid in the treatment and management of BBS.
Nephronophthisis and Senior-Loken Syndrome
Nephronophthisis (NPH) is the most common genetic cause of progressive renal failure in children and young adults. NPH is characterized by polyuria, growth retardation, and progressive deterioration of renal function with normal or slightly reduced kidney size (Hildebrandt et al. 1997. PubMed ID: 9326933; Hildebrandt et al. 2009. PubMed ID: 19118152). NPH is known as Senior-Loken syndrome (SLS), when associated with Leber congenital amaurosis (Otto et al. 2005. PubMed ID: 15723066; Hildebrandt et al. 2009. PubMed ID: 19118152).
Primary Ciliary Dyskinesia, Heterotaxy, Situs Inversus, and Kartagener's Syndrome
Primary ciliary dyskinesia (PCD) is a genetic disorder affecting the function of motile cilia (Leigh et al. 2009. PubMed ID: 19606528). The hallmark features of PCD are neonatal respiratory distress, chronic coughing, and recurrent sinus or ear infections; 80-100% of all PCD patients have one or more of these symptoms. In 20-50% of individuals with PCD, the major visceral organs are reversed from their normal positions, also called situs inversus (Sutherland and Ware. 2009. PubMed ID: 19876930). Kartagener’s syndrome is a condition defined by the symptomatic triad of situs inversus, sinusitis, and bronchiectasis. Patients with PCD can also have abnormal orientation of some organs but not others, a condition called situs ambiguus or heterotaxy (Kennedy et al. 2007. PubMed ID: 17515466). For more information, see GeneReviews (Zariwala et al. 2019. PubMed ID: 20301301).
Heterotaxy syndrome results from a failure to properly establish left-right asymmetry during embryogenesis. This results in an abnormal arrangement of thoracic or abdominal visceral organs or both, including the heart, lungs, liver, spleen, intestines, and stomach. Affected patients frequently have significant morbidity and mortality due to a wide variety of cyanotic congenital heart defects. Aside from cardiac malformations, common defects include asplenia or polysplenia, left-sided liver, right-sided stomach, gastrointestinal malrotation, and altered lung lobation. Classic heterotaxy, cardiac malformations and visceral laterality defects, has an estimated prevalence of 1 in 10,000 live births (Lin et al. 2000. PubMed ID: 11256661).
The ciliopathy disorders described above have been proposed to represent a single clinical entity, with a spectrum of overlapping symptoms and causative genes.
Joubert and Meckel-Gruber Syndromes
JSRD and MKS are genetically heterogeneous; JSRD is known to be caused by pathogenic variants in at least 33 different genes, and MKS is caused by pathogenic variants in at least 22 different genes (Hartill et al. 2017. PubMed ID: 29209597; Parisi and Glass. 2017. PubMed ID: 20301500; Knopp et al. 2015. PubMed ID: 26003401; Shaheen et al. 2016. PubMed ID: 27894351). Most of the genes reported to cause MKS have also been found to cause JSRD, with the exception of B9D2, KIF14, NPHP3, and TTC21B. In addition, all genes reported to cause MKS and JSRD play some role in the structure, function and maintenance of the primary cilia or basal body organelle (Hildebrandt et al. 2009. PubMed ID: 19118152). Thus, MKS and JSRD have been proposed to represent a single clinical entity, with a spectrum of overlapping symptoms and causative genes. JSRD and MKS are inherited in an autosomal recessive manner except when caused by variants in OFD1, which is inherited in an X-linked dominant manner.
BBS is a genetically heterogeneous disorder known to be caused by pathogenic variants in at least 25 different genes including ARL6/BBS3, BBIP1/BBS18, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CEP164, CEP290/BBS14, C8orf37, IFT27/BBS19, IFT74/BBS20, IFT172, LZTFL1/BBS17, MKKS/BBS6, MKS1/BBS13, NPHP1, SDCCAG8/BBS16, TRIM32/BBS11, TTC8/BBS8, TTC21B, and WDPCP/BBS15 (Forsythe and Beales. 2015. PubMed ID: 20301537; Leitch et al. 2008. PubMed ID: 18327255; Kim et al. 2010. PubMed ID: 20671153; Otto et al. 2010. PubMed ID: 20835237; Lindstrand et al. 2016. PubMed ID: 27486776; Heon et al. 2016. PubMed ID: 27008867; Bujakowska et al. 2015. PubMed ID: 25168386; Lindstrand et al. 2014. PubMed ID: 24746959). TMEM67 is included in this panel as it has been suggested to be a genetic modifier of the BBS phenotype (Leitch et al. 2008. PubMed ID: 18327255). BBS is marked by both intra- and inter-familial phenotypic variability. It has been suggested that BBS has an oligogenic inheritance pattern. The triallelism hypothesis states that three pathogenic alleles in two loci are necessary for BBS. This hypothesis attempts to explain variable expressivity and the observation that several individuals with BBS have been found to have a third rare, possibly pathogenic variant in a second BBS gene (Katsanis et al. 2001. PubMed ID: 11567139; Katsanis. 2004. PubMed ID: 14976158; Leitch et al. 2008. PubMed ID: 18327255). However, others have not found evidence for triallelic inheritance patterns in their cohorts (Smaoui et al. 2006. PubMed ID: 16877420; Abu-Safieh et al. 2012. PubMed ID: 22353939). In the majority of reported cases, two pathogenic variants in one gene are sufficient for BBS. However, the severity may be modulated by an additional hypomorphic or loss of function allele(s) at another locus. It is recommended to use an autosomal recessive inheritance model when counseling patients and their families (Forsythe and Beales. 2015. PubMed ID: 20301537).
Nephronophthisis and Senior-Loken Syndrome
NPH and SLS are genetically heterogeneous disorders that are inherited in an autosomal recessive manner. NPH and SLS are caused by pathogenic variants in genes encoding proteins involved in cilia/centrosome structure, maintenance, or function (Hildebrandt et al. 2009. PubMed ID: 19118152).
Primary Ciliary Dyskinesia
PCD is caused by defects in motile cilia. Planar motion cilia (i.e. from the respiratory tract, brain, and reproductive tract) consist of nine microtubule doublets that surround a central core of two microtubules (9+2 configuration). Rotary motion cilia (i.e., those in the embryonal node) lack the central core microtubules (9+0 configuration). All motile cilia have inner and outer dynein arms attached at regular intervals to the nine peripheral microtubule doublets, which serve as molecular motors that drive microtubule sliding. For 9+2 cilia, radial spokes form a signal-transduction scaffold between the peripheral dynein arms and the central-core microtubule pair, giving these cilia their characteristic planar (i.e., forward and backward) motion. Motile cilia are very complex structures composed of roughly 250 proteins (Ferkol and Leigh. 2006. PubMed ID: 17142159). To date, defects in over 50 genes have been reported to cause PCD, which is most commonly inherited in an autosomal recessive manner (Zariwala et al. 2019. PubMed ID: 20301301). Rarely, PCD has been found to be inherited in an X-linked manner due to loss-of-function variants in OFD1 or RPGR (Budny et al. 2006. PubMed ID: 16783569; Moore et al 2006. PubMed ID: 16055928). In addition, the INVS/NPHP2 gene has been associated with situs inversus either with or without biliary complications (Schön et al. 2002. PubMed ID: 11935322; Otto et al. 2003. PubMed ID: 12872123). Symptoms of cystic fibrosis can sometimes mimic those of PCD.
Heterotaxy, Situs Inversus and Kartagener's syndrome
Both PCD and heterotaxy are genetically heterogeneous. PCD can be caused by pathogenic variants in at least 50 genes and heterotaxy is caused by pathogenic variants in at least 40 genes (Zariwala et al. 2019. PubMed ID: 20301301). In addition, the INVS/NPHP2, ANKS6, PKD1L1, DNAH6, and DNAH9 genes have been associated with situs inversus or heterotaxy, either with or without biliary complications (Schön et al. 2002. PubMed ID: 11935322; Otto et al. 2003. PubMed ID: 12872123; Hoff et al. 2013. PubMed ID: 23793029; Vetrini et al. 2016. PubMed ID: 27616478; Li et al. 2016. PubMed ID: 26918822; Fassad. 2018. PubMed ID: 30471717). Thus, a common thread among all these genes is the association of laterality defects. ACVR2B, FOXH1, LEFTY2, NKX2-5 and NODAL genes are associated with autosomal dominant laterality defects, ZIC3 is associated with X-linked recessive heterotaxy, and AK7, ODAD2/ARMC4, ANKS6, CCDC103, ODAD1/CCDC114, CCDC39, CCDC40, ODAD3/CCDC151, CFAP53, CFAP298, DNAAF1, DNAAF2, DNAAF3, DNAAF5 (HEATR2), DNAH1, DNAI1, DNAI2, DNAH5, DNAH11, DNAL1, DNAAF4 (previously called DYX1C1), GAS8, HYDIN, INVS, LRRC6, MMP21, NME8, SPAG1, ODAD4/TTC25 and ZMYND10 are associated with autosomal recessive PCD with or without laterality defects. SMAD2 is associated with autosomal dominant congenital heart defects with or without heterotaxy. Heterozygous nonsense and missense variants in GDF1 were identified in individuals with conotruncal heart defects (TOF, DORV, TGA) without visceral laterality defects (Karkera et al. 2007. PubMed ID: 17924340). Two truncating variants in GDF1 were found to cause classic heterotaxy in one Finnish family. Heterozygous carriers were asymptomatic (Kaasinen et al. 2010. PubMed ID: 20413652).
Clinical Sensitivity - Sequencing with CNV PGxome
Clinical sensitivity for BBS is ~80% (Forsythe and Beales. 2015. PubMed ID: 20301537; Lindstrand et al. 2016. PubMed ID: 27486776).
Clinical sensitivity for Joubert syndrome and related disorders is 62%-94% (Parisi and Glass. 2017. PubMed ID: 20301500) and 50%-77% for Meckel-Gruber syndrome (Knopp et al. 2015. PubMed ID: 26003401; Hartill et al. 2017. PubMed ID: 29209597).
Clinical sensitivity for nephronophthisis is approximately 30% overall (Hildebrandt et al. 2009. PubMed ID: 19118152). Approximately 20% of individuals with nephronophthisis have a homozygous deletion encompassing the NPHP1 gene (Hoefele et al 2005. PubMed ID: 15776426; Hildebrandt et al 2009. PubMed ID: 19118152). This NGS test can detect the ~279 kb common NPHP1 deletion.
Clinical sensitivity for PCD is ~80% (Zariwala et al. 2019. PubMed ID: 20301301).
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This panel typically provides 95.8% 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.
Due to technical difficulties, only exons 1-5 and 85-86 of the HYDIN gene are included in this panel.
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
This test is for patients with symptoms overlapping one or more of the ciliopathy disorders.
This test is for patients with symptoms overlapping one or more of the ciliopathy disorders.
|Bardet-Biedl Syndrome (BBS) Panel|
|Joubert and Meckel-Gruber Syndromes Panel|
|Nephronophthisis and Senior-Loken Syndrome Panel|
- Abu-Safieh et al. 2012. PubMed ID: 22353939
- Alexiev et al. 2006. PubMed ID: 16879033
- Brancati et al. 2010. PubMed ID: 20615230
- Budny et al. 2006. PubMed ID: 16783569
- Bujakowska et al. 2015. PubMed ID: 25168386
- Chaumoitre et al. 2006. PubMed ID: 17094077
- Doherty. 2009. PubMed ID: 19778711
- Elbedour et al. 1994. PubMed ID: 7802002
- Fassad. 2018. PubMed ID: 30471717
- Ferkol and Leigh. 2006. PubMed ID: 17142159
- Forsythe and Beales. 2015. PubMed ID: 20301537
- Green et al. 1989. PubMed ID: 2779627
- Hartill et al. 2017. PubMed ID: 29209597
- Heon et al. 2016. PubMed ID: 27008867
- Hildebrandt et al. 1997. PubMed ID: 9326933
- Hildebrandt et al. 2009. PubMed ID: 19118152
- Hoefele et al. 2005. PubMed ID: 15776426
- Hoff et al. 2013. PubMed ID: 23793029
- Kaasinen et al. 2010. PubMed ID: 20413652
- Karkera et al. 2007. PubMed ID: 17924340
- Katsanis et al. 2001. PubMed ID: 11567139
- Katsanis. 2004. PubMed ID: 14976158
- Kennedy. et al. 2007. PubMed ID: 17515466
- Kim et al. 2010. PubMed ID: 20671153
- Knopp et al. 2015. PubMed ID: 26003401
- Leigh et al. 2009. PubMed ID: 19606528
- Leitch et al. 2008. PubMed ID: 18327255
- Li et al. 2016. PubMed ID: 26918822
- Lin et al. 2000. PubMed ID: 11256661
- Lindstrand et al. 2014. PubMed ID: 24746959
- Lindstrand et al. 2016. PubMed ID: 27486776
- Moore et al. 2006. PubMed ID: 16055928
- Otto et al. 2003. PubMed ID: 12872123
- Otto et al. 2005. PubMed ID: 15723066
- Otto et al. 2010. PubMed ID: 20835237
- Parisi and Glass. 2017. PubMed ID: 20301500
- Parisi et al. 2007. PubMed ID: 17377524
- Schön et al. 2002. PubMed ID: 11935322
- Shaheen et al. 2016. PubMed ID: 27894351
- Sheffield. 2010. PubMed ID: 20697559
- Smaoui et al. 2006. PubMed ID: 16877420
- Sutherland and Ware. 2009. PubMed ID: 19876930
- Vetrini et al. 2016. PubMed ID: 27616478
- Zariwala et al. 2019. PubMed ID: 20301301
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.
- 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 Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
ORDER OPTIONSView Ordering Instructions
1) Select Test Method (Backbone)
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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.