TRPV4-related Disorders via the TRPV4 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11775 | TRPV4 | 81479 | 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.
Clinical Features and Genetics
Clinical Features
TRPV4 encodes transient receptor potential cation channel, subfamily V, member 4, is a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels. The encoded protein is a calcium permeable nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure (Vriens et al. Proc Natl Acad Sci 101:396-401, 2004). TRPV4 is involved in many different cellular functions; it has an important role in differentiation of chondrocytes and terminal differentiation of osteoclasts via calcium influx (Muramatsu et al. J Biol Chem 282:32158-32167, 2007; Masuyama et al. Cell Metab 8:257-265, 2008).
|
Phenotype |
Inheritance pattern |
OMIM# |
|
Hereditary motor and sensory neuropathy, type IIc (HMSN2C) |
Autosomal dominant |
606071 |
|
Scapuloperoneal spinal muscular atrophy (SPSMA) |
Autosomal dominant |
181405 |
|
Metatropic dysplasia (MD) |
Autosomal dominant |
156530 |
|
Parastremmatic dysplasia |
Autosomal dominant |
168400 |
|
Brachyolmia type 3 |
Autosomal dominant |
113500 |
|
Spondyloepimetaphyseal dysplasia, Maroteaux type |
Autosomal dominant |
184095 |
|
Spondylometaphyseal dysplasia, Kozlowski type (SMDK) |
Autosomal dominant |
184252 |
|
Familial digital arthropathy with brachydactyly |
Autosomal dominant |
606835 |
Genetics
Variants in TRPV4 are known to cause at least 8 distinct phenotypes. The majority of these variants are missense resulting in gain-of-function (Rock et al. Nat Genet 40:999-1003, 2008; Deng et al. Nat Genet 42:165-169, 2010) or haploinsufficiency (Auer-Grumbach et al. Nat Genet 42:160-164, 2010).
Clinical Sensitivity - Sequencing with CNV PGxome
This test is predicted to detect disease variants in virtually all individuals with a clinical diagnosis of MD, SMDK, and SED Maroteaux type (Camacho et al. Am J Med Genet 152A:1169–1177, 2010; Nishimura et al. Am J Med Genet 152A:1443–1449, 2010; Dai et al. J Med Genet 47: 704-709, 2010; Krakow et al. Am J Hum Genet 84: 307-315, 2009). Testing of large series of patients with other TRPV4-related phenotypes has not yet been reported.
Testing Strategy
This test provides full coverage of all coding exons of the TRPV4 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
Candidates for this test are patients with clinical and radiographic features consistent with TRPV4-related phenotypes, and family members of patients who have a known TRPV4 variant.
Candidates for this test are patients with clinical and radiographic features consistent with TRPV4-related phenotypes, and family members of patients who have a known TRPV4 variant.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| TRPV4 | 605427 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
Citations
- Auer-Grumbach, M., et.al. (2010). "Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C." Nat Genet 42(2): 160-4. PubMed ID: 20037588
- Camacho, N., et.al. (2010). "Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia." Am J Med Genet A 152A(5): 1169-77. PubMed ID: 20425821
- Dai, J., et.al. (2010). "Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family." J Med Genet 47(10): 704-9. PubMed ID: 20577006
- Deng, H. X., et.al. (2010). "Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4." Nat Genet 42(2): 165-9. PubMed ID: 20037587
- Krakow, D., et.al. (2009). "Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia." Am J Hum Genet 84(3): 307-15. PubMed ID: 19232556
- Masuyama, R., et.al. (2008). "TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts." Cell Metab 8(3): 257-65. PubMed ID: 18762026
- Muramatsu, S., et.al. (2007). "Functional gene screening system identified TRPV4 as a regulator of chondrogenic differentiation." J Biol Chem 282(44): 32158-67. PubMed ID: 17804410
- Nishimura, G., et.al. (2010). "Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations." Am J Med Genet A 152A(6): 1443-9. PubMed ID: 20503319
- Rock, M. J., et.al. (2008). "Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia." Nat Genet 40(8): 999-1003. PubMed ID: 18587396
- Vriens, J., et.al. (2004). "Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4." Proc Natl Acad Sci U S A 101(1): 396-401. PubMed ID: 14691263
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
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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ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.