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Autosomal Dominant Cone Dystrophy 3 (COD3) and Cone-Rod Dystrophy 14 (CRD14) via the GUCA1A 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
GUCA1A 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9065GUCA1A81479 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


  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Hereditary cone dystrophies (COD) are clinically and genetically heterogeneous disorders that result in the dysfunction of the cone photoreceptors. Major clinical features include bilateral visual loss, abnormal color vision, central scotomata, variable degrees of nystagmus and photophobia. CODs manifest as progressive or stationary disorders. The stationary subtype CODs occur within the first months of life with pendular nystagmus and photophobia with normal rod function and are better described as cone dysfunction syndromes, whereas progressive CODs usually occur in childhood or early adulthood and patients often develop rod photoreceptor dysfunction in later life. The stationary subtype CODs are uncommon with an incidence of about 1 in 30,000 (Michaelides et al., 2004; Simunovic and Moore, 1998).

Cone rod dystrophies (CORDs/CRDs) are also rare with a worldwide prevalence of ~1 in 40,000. CORDs are characterized by dysfunction or degeneration of cone photoreceptors with relative preservation of rod function in the initial stages. The most common symptoms are photophobia and epiphora in bright light, decreased visual acuity, and dyschromatopsia. Fundus changes may vary from mild pigment granularity to a distinct atrophic lesion in the central macula. As the disease progresses, degeneration of rod photoreceptors also occurs and leads to progressive night blindness and peripheral visual field loss (Hamel, 2007).

COD and CRD are diagnosed mainly on the basis of photopic and scotopic electroretinogram responses, fundoscopy and optical coherence tomography (Jiang and Baehr, 2010).


Both COD and CRD exhibit autosomal dominant (ad), autosomal recessive (ar) or X-linked (XL) inheritance. (RetNet). Thus far, the best characterized genes associated with ad COD and CRD are GUCY2D, encoding photoreceptor guanylate cyclase 1 (retGC-1 or GC1), and GUCA1A, encoding the Ca2+-binding protein (GCAP1), which are expressed in the outer segments of the photoreceptors (Jiang and Baehr, 2010). GC1 and GCAP1 play major roles in visual phototransduction, which is a biochemical process responsible for light conversion into electrical signals in the rod and cone cells. In this process, GC1 helps in restoring photoreceptor sensitivity by synthesizing cyclic guanosine monophosphate (cGMP), which is regulated by guanylate cyclase activator proteins (GCAPs: 1 and 2). GCAPs are sensitive to changes in the cytoplasmic Ca2+ concentrations. It has been reported that GCAP2 is activated at lower Ca2+ concentrations than GCAP1 (Hwang et al., 2003). However, GCAP1 and GCAP2 regulate the Ca2+ signaling of GC1 in different ways. At lower cytoplasmic Ca2+ concentrations, GCAP1 interacts with GC1 and stimulates it, and consequently, the cGMP level is restored (Jiang et al., 2005). Even in the absence of GCAP2, GCAP1alone can restore rod and cone responses, whereas GCAP2 can only partially compensate (Kitiratschky et al., 2009). Thus, GCAP1 plays a major role in regaining the dark-adapted state after excitation of the photoreceptor (Mendez et al., 2001; Pennesi et al., 2003). Disruption of Ca2+ homeostasis, due either to genetic or environmental factors leads to apoptosis of the photoreceptor cells (Baehr and Palczewski., 2007; Garcia-Hoyos et al., 2011). So far, about ten causative mutations (mostly missense) in GUCA1A have been associated with adCOD and adCRD (The Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

A mutation analysis in an American five-generation pedigree with 30 living family members identified heterozygous GUCA1A mutations in all affected family members (11/30; ~36%), which segregated with the disease phenotype and was not found in 200 normal controls (Jiang et al., 2005). Another mutation screening in a three-generation Spanish family with ad retinal dystrophy detected a GUCA1A mutation in all affected individuals (5/9; ~55%), which also co-segregated with the disease phenotype and was not found in 200 ethnically matched control individuals (Kamenarova et al., 2013). In another study with 24 unrelated patients (19 patients had adCOD and five patients had adCRD) GUCA1A mutations were identified in four patients (4/24; ~16%) (Kitiratschky et al., 2009). The GUCA1A gene was analyzed in 216 patients with various hereditary retinal disorders in which cones were dysfunctional and five causative mutations in a total of six patients were identified (6/216; ~3%) (Nishiguchi et al., 2004).

So far, no gross deletions or duplications have been reported in GUCA1A (The Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the GUCA1A 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

All patients with symptoms suggestive of adCOD and adCRD, especially patients with distinctive electrophysiological findings (please see the clinical features section).


Official Gene Symbol OMIM ID
GUCA1A 600364
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Cone Dystrophy 3 AD 602093
Cone-rod dystrophy 14 AD 602093

Related Test

Cone-Rod Dystrophy Panel


  • Baehr W and Palczewski K. 2007. Guanylate cyclase-activating proteins and retina disease. Subcell Biochem 45:71-91. PubMed ID: 18193635
  • Garcia-Hoyos M, Auz-Alexandre CL, Almoguera B, Cantalapiedra D, Riveiro-Alvarez R, Lopez-Martinez MA, Gimenez A, Blanco-Kelly F, Avila-Fernandez A, Trujillo-Tiebas MJ, Garcia-Sandoval B, Ramos C, Ayuso C. 2011. Mutation analysis at codon 838 of the Guanylate Cyclase 2D gene in Spanish families with autosomal dominant cone, cone-rod, and macular dystrophies. Mol. Vis. 17:1103-1109. PubMed ID: 21552474
  • Hamel CP. 2007. Cone rod dystrophies. Orphanet J Rare Dis 1;2:7. PubMed ID: 17270046
  • Human Gene Mutation Database (Bio-base).
  • Hwang JY, Lange C, Helten A, Höppner-Heitmann D, Duda T, Sharma RK, Koch KW. 2003. Regulatory modes of rod outer segment membrane guanylate cyclase differ in catalytic efficiency and Ca(2+)-sensitivity. Eur. J. Biochem. 270: 3814–3821. PubMed ID: 12950265
  • Jiang L, Baehr W. 2010. GCAP1 Mutations Associated with Autosomal Dominant Cone Dystrophy. In: Anderson RE, Hollyfield JG, and LaVail MM, editors. Retinal Degenerative Diseases, New York, NY: Springer New York, p 273–282. PubMed ID: 20238026
  • Jiang L, Katz BJ, Yang Z, Zhao Y, Faulkner N, Hu J, Baird J, Baehr W, Creel DJ, Zhang K. 2005. Autosomal dominant cone dystrophy caused by a novel mutation in the GCAP1 gene (GUCA1A). Mol. Vis. 11:143-51. PubMed ID: 15735604
  • Kamenarova K, Corton M, García-Sandoval B, Fernández-San Jose P, Panchev V, Ávila-Fernández A, López-Molina MI, Chakarova C, Ayuso C, Bhattacharya SS. 2013. Novel GUCA1A Mutations Suggesting Possible Mechanisms of Pathogenesis in Cone, Cone-Rod, and Macular Dystrophy Patients. BioMed Research International 2013: 1–15. PubMed ID: 24024198
  • Kitiratschky VB, Behnen P, Kellner U, Heckenlively JR, Zrenner E, Jägle H, Kohl S, Wissinger B, Koch K-W. 2009. Mutations in the GUCA1A gene involved in hereditary cone dystrophies impair calcium-mediated regulation of guanylate cyclase. Human mutation 30: E782–E796. PubMed ID: 19459154
  • Mendez A, Burns ME, Sokal I, Dizhoor AM, Baehr W, Palczewski K, Baylor DA, Chen J. 2001. Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors. Proceedings of the National Academy of Sciences 98:9948-9953. PubMed ID: 11493703
  • Michaelides M. 2004. The cone dysfunction syndromes. British Journal of Ophthalmology 88: 291–297. PubMed ID: 14736794
  • Nishiguchi KM. 2004. A Novel Mutation (I143NT) in Guanylate Cyclase-Activating Protein 1 (GCAP1) Associated with Autosomal Dominant Cone Degeneration. Investigative Ophthalmology & Visual Science 45: 3863–3870. PubMed ID: 15505030
  • Pennesi ME, Howes KA, Baehr W, Wu SM. 2003. Guanylate cyclase-activating protein (GCAP) 1 rescues cone recovery kinetics in GCAP1/GCAP2 knockout mice. Proceedings of the National Academy of Sciences 100: 6783–6788. PubMed ID: 12732716
  • RetNet
  • Simunovic MP, Moore AT. 1998. The cone dystrophies. Eye (Lond) 12 ( Pt 3b):553-565. PubMed ID: 9775217


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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