• Test code: 05314
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Dyskeratosis Congenita Panel

Test description

The Invitae Dyskeratosis Congenita Panel analyzes genes associated with dyskeratosis congenita (DC). DC is a clinically and genetically heterogeneous telomere disorder characterized by abnormal skin pigmentation, nail dystrophy, oral leukoplakia and increased risk of progressive bone marrow failure and malignancies. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive panel for DC.

The primary panel includes 9 genes that are associated with DC. In addition to the primary panel, clinicians can also choose to include 3 genes that have preliminary evidence of an association with DC. These genes were selected from a review of the literature and expert recommendations. At this time, the association of these genes with DC remains uncertain; however, some clinicians may wish to include genes that may prove to be clinically significant in the future. These genes can be added at no additional charge.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations.

If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept DNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for DNA samples because the success rate varies based on sample quality. Please see our Specimen requirements page for more details.

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Primary panel (9 genes)


Add-on Preliminary-evidence Genes for Dyskeratosis Congenita (3 genes)

Genes with preliminary evidence of association with dyskeratosis congenita are available to add on to the primary panel. Adding on preliminary-evidence genes can increase the number of variants of uncertain significance that are identified. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


  • dyskeratosis congenita
    • Hoyeraal-Hreidarsson syndrome
    • Revesz syndrome
    • Coats plus syndrome

DC is a telomere disorder classically characterized by dysplastic nails, lacy reticular pigmentation and oral leukoplakia. Reduced penetrance is common, so some affected individuals might not have these symptoms. DC is associated with an increased risk of progressive bone marrow failure, myelodysplastic syndrome, acute myelogenous leukemia, solid tumors and pulmonary fibrosis. Other findings include abnormal pigmentation changes, eye abnormalities and dental anomalies. The age of onset is variable and disease presentation can be mild to severe.

Individuals with pathogenic variants in the CTC1 gene may have additional symptoms including leukoencephalopathy, brain calcifications and cysts.

A pathogenic variant has been identified in approximately 50% of individuals who meet the clinical diagnostic criteria for DC.

GeneAttribution to DC
CTC1 1%–3%
DKC1 17%–36%
NHP2 <1%
NOP10 <1%
RTEL1 2%-8%
TERC 6%–10%
TERT 1%–7%
TINF2 11%–24%

The inheritance of DC varies by gene:

  • autosomal dominant: TERC, TINF2
  • autosomal recessive: CTC1, NHP2, NOP10, PARN, RTEL1
  • autosomal dominant or autosomal recessive: TERT
  • X-linked: DKC1

The clinical expression of DC is highly variable, even among family members, and the exact penetrance is unclear. However, abnormally short telomeres have been consistently demonstrated in individuals with pathogenic variants in causative genes, regardless of clinical phenotype. (PMID: 22058220)

The prevalence is unknown.

Testing for DC should be considered in individuals with a personal history of:

  • clinical features of DC (particularly dysplastic nails, lacy reticular pigmentation and oral leukoplakia)
  • progressive bone marrow failure at any age
  • myelodysplastic syndrome or acute myeloid leukemia presenting at an unusually young age
  • solid tumors of the head, neck, or anogenital area in individuals <50 years old
  • pulmonary fibrosis
  • shortened telomere length
  • a family history of DC

If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, but deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.

  1. Savage, SA, et al. Dyskeratosis congenita: the first NIH clinical research workshop. Pediatr Blood Cancer. 2009; 53(3):520-3. PMID: 19415736
  2. Alter, BP, et al. Cancer in dyskeratosis congenita. Blood. 2009; 113(26):6549-57. PMID: 19282459
  3. Fernández, García, MS, Teruya-Feldstein, J. The diagnosis and treatment of dyskeratosis congenita: a review. J Blood Med. 2014; 5:157-67. PMID: 25170286
  4. Keller, RB, et al. CTC1 Mutations in a patient with dyskeratosis congenita. Pediatr Blood Cancer. 2012; 59(2):311-4. PMID: 22532422
  5. Dokal, I, et al. Clinical utility gene card for: dyskeratosis congenita. Eur. J. Hum. Genet. 2011; 19(11):None. PMID: 21610750
  6. Vulliamy, TJ, et al. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. 2006; 107(7):2680-5. PMID: 16332973
  7. Savage, SA, Bertuch, AA. The genetics and clinical manifestations of telomere biology disorders. Genet. Med. 2010; 12(12):753-64. PMID: 21189492
  8. Alter, BP, et al. Telomere length is associated with disease severity and declines with age in dyskeratosis congenita. Haematologica. 2012; 97(3):353-9. PMID: 22058220
  9. Keel SB, et al. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. Haematologica. 2016;101(11):1343-1350. PMID: 27418648
  10. Ballew BJ, et al. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol. 2013;6(3):327-37. PMID: 23782086
  11. Dokal I, et al. Clinical utility gene card for: Dyskeratosis congenita - update 2015. Eur J Hum Genet. 2015;23(4) PMID: 25182133
  12. Savage, SA. Dyskeratosis Congenita. 2009 Nov 12. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301779
  13. Ballew, BJ, et al. Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita. Hum. Genet. 2013; 132(4):473-80. PMID: 23329068
  14. Stuart, BD, et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat. Genet. 2015; 47(5):512-7. PMID: 25848748
  15. Körner, CG, et al. The deadenylating nuclease (DAN) is involved in poly(A) tail removal during the meiotic maturation of Xenopus oocytes. EMBO J. 1998; 17(18):5427-37. PMID: 9736620
  16. Walne, AJ, et al. Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. Am. J. Hum. Genet. 2013; 92(3):448-53. PMID: 23453664

Clinical management of DC patients is complex and requires comprehensive coordinated care among specialties. Recommendations for management have been discussed at a DC clinical research workshop held at the NIH in 2008:

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ACD NM_001082486.1
CTC1 NM_025099.5
DKC1 NM_001363.4
NHP2 NM_017838.3
NOP10 NM_018648.3
PARN NM_002582.3
RTEL1 NM_001283009.1
TERC NR_001566.1
TERT NM_198253.2
TINF2 NM_001099274.1
USB1 NM_024598.3
WRAP53 NM_018081.2