Clinical Genomics

XomeDx

XomeDx - Whole Exome Sequencing (Proband)

Forms and Documents

Test Details

  • Determination of a clinical diagnosis
  • Identification of gene implicated in genetic disease
  • Recurrence risk assessment

XomeDx, or exome sequencing (ES), can be used to identify the underlying molecular basis of a genetic disorder in an affected individual and is best suited for patients who have a genetic condition that routine genetic testing has not been able to identify. The XomeDx test targets exons, which are the protein-coding regions of the human genome. Exons are captured and sequenced using massively parallel sequencing.

XomeDx and XomeDxPlus test reports will include analysis of ACMG secondary findings in the proband unless the proband is opted-out. The presence of any secondary finding(s) reported for the proband will be provided for all relatives tested by XomeDx or XomeDxPlus. GeneDx does not conduct an independent evaluation of secondary findings in relatives as part of the proband’s XomeDx test.

  • Next-Gen Sequencing

Ordering

561b
8-12 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81415
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Singleton AB. Exome sequencing: a transformative technology. Lancet Neurol. 2011 Oct;10(10):942-6.
  2. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Exome sequencing
  3. Ku CS, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet. 2011 Apr;129(4):351-70. Epub 2011 Feb 18.
  4. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011 Sep 27;12(11):745-55.
XomeDxPlus (Proband)

Forms and Documents

Test Details

  • Determination of a clinical diagnosis
  • Identification of gene implicated in genetic disease
  • Recurrence risk assessment

XomeDxPlus includes whole exome sequencing as well as mitochondrial genome sequencing and deletion testing. For more information on the mitochondrial genome sequencing and deletion component of the XomeDxPlus testing, please visit our neurology/mitochondrial genetics page on our website. XomeDxPlus is best suited for individuals with clinical features suggesting a mitochondrial disorder.

  • Next-Gen Sequencing

Ordering

690b
8-12 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81415, 81460
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Singleton AB. Exome sequencing: a transformative technology. Lancet Neurol. 2011 Oct;10(10):942-6.
  2. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Exome sequencing
  3. Ku CS, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet. 2011 Apr;129(4):351-70. Epub 2011 Feb 18.
  4. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011 Sep 27;12(11):745-55.
XomeDx - Whole Exome Sequencing (Trio)

Forms and Documents

Test Details

  • Determination of a clinical diagnosis
  • Identification of gene implicated in genetic disease
  • Recurrence risk assessment

XomeDx, or exome sequencing (ES), can be used to identify the underlying molecular basis of a genetic disorder in an affected individual and is best suited for patients who have a genetic condition that routine genetic testing has not been able to identify. The XomeDx test targets exons, which are the protein-coding regions of the human genome. Exons are captured and sequenced using massively parallel sequencing.

XomeDx and XomeDxPlus test reports will include analysis of ACMG secondary findings in the proband unless the proband is opted-out. The presence of any secondary finding(s) reported for the proband will be provided for all relatives tested by XomeDx or XomeDxPlus. GeneDx does not conduct an independent evaluation of secondary findings in relatives as part of the proband’s XomeDx test.

  • Next-Gen Sequencing

Ordering

561a
8-12 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81415x1, 81416x2
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Singleton AB. Exome sequencing: a transformative technology. Lancet Neurol. 2011 Oct;10(10):942-6.
  2. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Exome sequencing
  3. Ku CS, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet. 2011 Apr;129(4):351-70. Epub 2011 Feb 18.
  4. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011 Sep 27;12(11):745-55.
XomeDxPlus (Trio)

Forms and Documents

Test Details

  • Determination of a clinical diagnosis
  • Identification of gene implicated in genetic disease
  • Recurrence risk assessment

XomeDxPlus includes whole exome sequencing as well as mitochondrial genome sequencing and deletion testing. For more information on the mitochondrial genome sequencing and deletion component of the XomeDxPlus testing, please visit our neurology/mitochondrial genetics page on our website. XomeDxPlus is best suited for individuals with clinical features suggesting a mitochondrial disorder.

  • Next-Gen Sequencing

Ordering

690a
8-12 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81415, 81416x2, 81460
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Singleton AB. Exome sequencing: a transformative technology. Lancet Neurol. 2011 Oct;10(10):942-6.
  2. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Exome sequencing
  3. Ku CS, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet. 2011 Apr;129(4):351-70. Epub 2011 Feb 18.
  4. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011 Sep 27;12(11):745-55.

XomeDxXpress

XomeDxXpress (WES with a Verbal Result in 7 Days)

Forms and Documents

Test Details

  • Determination of a clinical diagnosis
  • Identification of gene implicated in genetic disease
  • Recurrence risk assessment

The XomeDxXpress test (Trio only) is whole exome sequencing with an expedited turnaround time (TAT) of approximately 2 weeks. A verbal result is given within 7 calendar days after the start of testing and will include pathogenic and/or expected pathogenic variants in known disease-causing genes (Human Genome Mutation Database genes). A written report including all clinically relevant, confirmed variants will be reported within approximately 2 weeks after the start of testing. Because of the rapid TAT, blood or DNA samples on the proband and both biological parents must be submitted at the same time, along with clinical information, in order to begin testing. This test requires approval by GeneDx; please email Xpress@GeneDx.com to discuss prior to sending in samples.

  • Next-Gen Sequencing

Ordering

896
Verbal result in 7 days, Final Report ~2 weeks
3-6 mL Blood Only - Lavender Top Tube
Ug DNA Concentration

Billing

81415, 81416x2
Yes
No
* For price inquiries please email zebras@genedx.com

References

  1. Bamshad et al. (2011) Nature Reviews Genetics. 12:745-755
  2. Green et al. (2013) Genet Med 15:565-57.

XomeDxPrenatal

XomeDxPrenatal Targeted

Forms and Documents

Test Details

  • Establishing a molecular diagnosis in a fetus with abnormal ultrasound findings.

With a turnaround time (TAT) of 3-4 weeks, the fetal specimen and specimens from both biological parents must be submitted at the same time, along with clinical information, in order to begin testing. This test requires approval by GeneDx before ordering; please e-mail WESPrenatal@genedx.com to discuss cases prior to submitting samples.

The XomeDxPrenatal Targeted fetal report will include medically relevant pathogenic or likely pathogenic variants in genes expected to be related to the reported fetal phenotype. Variants of uncertain significance may be reported if there is compelling evidence to suggest clinical significance.

  • Next-Gen Sequencing

Ordering

959
3-4 weeks
30 mL Amniotic Fluid
30 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|15 µg DNA Concentration

Billing

81415, 81416x2, 81265
Yes
No
* For price inquiries please email zebras@genedx.com
XomeDxPrenatal Comprehensive

Forms and Documents

Test Details

  • Establishing a molecular diagnosis in a fetus with abnormal ultrasound findings

With a turnaround time (TAT) of 3-4 weeks, the fetal specimen and specimens from both biological parents must be submitted at the same time, along with clinical information, in order to begin testing. This test requires approval by GeneDx before ordering; please e-mail WESPrenatal@genedx.com to discuss cases prior to submitting samples.

The XomeDxPrenatal Comprehensive fetal report will also include medically relevant pathogenic or likely pathogenic variants in genes expected to be related to the reported fetal phenotype. Variants of uncertain significance may be reported if there is compelling evidence to suggest clinical significance. In addition, variants of uncertain significance in novel candidate genes may be reported.

  • Next-Gen Sequencing

Ordering

J499
3-4 weeks
30 mL Amniotic Fluid
30 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|15 µg DNA Concentration

Billing

81415, 81416x2, 81265
Yes
No
* For price inquiries please email zebras@genedx.com

XomeDxSlice

Congenital Ichthyosis XomeDxSlice

Forms and Documents

Test Details

ABCA12, ABHD5, AGPS, ALDH3A2, ALOX12B, ALOXE3, AP1S1, ARSE, CASP14, CERS3, CLDN1, CYP4F22, EBP, ELOVL4, FLG, GJB2 (Cx26), GJB3 (Cx31), GJB4 (Cx30.3), GJB6 (Cx30), KRT1, KRT10, KRT2, KRT9, LIPN, LOR, NIPAL4(Ichthyin), PEX7, PHGDH, PHYH, PNPLA1, PNPLA2, POMP, PSAT1, SDR9C7, SLC27A4, SNAP29, SPINK5, ST14, STS, TGM1, TGM5, VPS33B, ZMPSTE24
  • Identification of the specific molecular basis of congential ichthyosis or related skin disorders
  • Genetic counseling and recurrence risk assessment
  • Option for prenatal testing in future pregnancies

As needed, based on the referring diagnosis and coverage achieved by the XomeDxSlice-Ichthyosis for a given patient, critical exons with a high yield of mutations will be filled-in by dideoxy sequencing. For any autosomal recessive gene, if one definitive mutation is found by XomeDxSlice sequencing, AND the gene fits the type of ichthyosis reported by the referring physician, capillary sequencing will be used to fill in sequence for exons that are not sufficiently covered (>10X) to find the second mutation. If no second mutation is found by sequencing, deletion/duplication analysis of that gene can be performed at no additional cost can be performed at no additional cost.

Patient samples sent for XomeDxSlice will not be evaluated for secondary findings and therefore will not receive secondary findings as part of their result.\\\\\\\\\\\\\\\"

  • Next-Gen Sequencing

Ordering

708
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81252x1, 81254x1, 81401x1, 81479x1
Yes
Yes
* For price inquiries please email zebras@genedx.com
Epidermolysis Bullosa (EB) XomeDxSlice

Forms and Documents

Test Details

CD151, CDSN, CHST8, COL17A1, COL7A1, CSTA, DSG1, DSG2, DSG3, DSG4, DSP, DST, EXPH5, FERMT1, GRIP1, ITGA3, ITGA6, ITGB4, KLHL24, KRT1, KRT10, KRT14, KRT5, LAMA3, LAMB3, LAMC2, MMP1, NID1, PKP1, PLEC, TGM5
  • Identification of the specific molecular basis of a hereditary blistering disorder
  • Recurrence risk assessment
  • Preparation for prenatal testing in future pregnancies

If an affected individual is found by XomeDxSlice-EB to have only a single mutation in a gene with recessive inheritance, deletion/duplication analysis of that gene can be performed at no additional cost.

Patient samples sent for XomeDxSlice will not be evaluated for secondary findings and therefore will not receive secondary findings as part of their result.

  • Next-Gen Sequencing

Ordering

707
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81406x2, 81479x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Varki et al., 2006 J Med Genet 43:641-52
  2. Varki et al., 2007 J Med Genet. 44:181-92
  3. Schumann et al., 2013 Br J Dermatol. Mar 18
  4. Charlesworth et al., 2013 Br J Dermatol. 168:808-814
  5. Yang et al., 2012 PediatrDermatol. 29:725-31
  6. Has et al., 2012 N Engl J Med. 366:1508-14
  7. Liu et al., 2012 J Invest Dermatol. 132:742-4
  8. Smith 2012 Br J Dermatol. 166:894-6
  9. Has et al., 2011 Hum Mutat. 32:1204-12
  10. Murase et al., 2011Acta DermVenereol. 91:730-1
  11. Uitto J. 2011 ActaDermVenereol. 91:259-61
  12. Almaani et al., 2011 ActaDermVenereol. 91:262-6
  13. Kiritsi et al., 2011 J Med Genet. 48:450-7
  14. Techanukul et al., 2011 ActaDermVenereol. 91:267-70
  15. Pigors et al., 2011 Hum Mol Genet. 20:1811-9
  16. Natsuga et al., 2010 Hum Mutat. 31:1687-98
  17. Hobbs et al., 2010 J Invest Dermatol. 130:2680-3
  18. Fine et al., 2008 J Am AcadDermatol. 58:931-50
  19. Intong et al., 2012 ClinDermatol. 30:70-7
  20. Sprecher E. 2010 DermatolClin. 2028:23-32
  21. Rezniczek et al., 2010 DermatolClin. 28:33-41, A series of review articles in DermatolClin. 2010 Jan;28
  22. Dang et al., 2008 ExpDermatol. 17:553-68
  23. Pfendner EG, Lucky AW Junctional Epidermolysis Bullosa. In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews
  24. Seattle (WA): University of Washington, Seattle; 1993-2008, Pfendner EG, Lucky AW: Dystrophic Epidermolysis Bullosa (November 2010) in: GeneReviews at GeneTests: Medical Genetics Information Resource [database online] Copyright, University of Washington,
  25. Pfendner EG & Lucky AW: Epidermolysis Bullosa with Pyloric Atresia (February 2013) in: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2010. Available at http://www.gene
Custom XomeDxSlice (1-150 Genes, Proband Only)

Forms and Documents

Test Details

  • For smaller custom gene lists of 1-150 genes for proband-only analysis
  • For analysis of genes within regions of homozygosity detected by whole genome array
  • Identification of underlying molecular cause of clinical diagnosis
  • Recurrence risk assessment
  • Next-Gen Sequencing

Ordering

706
8 weeks
2-5 mL Blood - Lavender Top Tube

Billing

Varies by Genes
Yes
Yes
* For price inquiries please email zebras@genedx.com
Custom XomeDxSlice Xpanded (>150 Genes, Trio Optional)

Forms and Documents

Test Details

  • For large custom gene lists of 150 or more genes as proband-only or trio analysis
  • Identification of underlying molecular cause of clinical diagnosis
  • Recurrence risk assessment
  • Next-Gen Sequencing

Ordering

J757
8 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab

Billing

Varies by Genes
Yes
Yes
* For price inquiries please email zebras@genedx.com

XomeDxInsights

XomeDxInsights

Forms and Documents

Test Details

  • Learn about medically relevant risk to have or develop certain genetic conditions

XomeDxInsights is an exome sequencing (ES) service designed for generally healthy adults who would like to learn about medically relevant changes in their genetic code, and their risk to have or develop certain genetic conditions. This test provides information in three primary health categories: personal health, reproductive risk, and pharmacogenomics.

Please note that XomeDxInsights requires two tubes of blood.

  • Next-Gen Sequencing

Ordering

J775
10 weeks
8-10 mL Blood - Lavender Top Tube (2 tubes)

Billing

81415
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Amiri-Yekta et al. (2016) Hum. Reprod. 31 (12):2872-2880 (PMID: 27798045)
  2. Bamshad et al. (2011) Nature Reviews. Genetics 12 (11):745-55 (PMID: 21946919)
  3. Committee Opinion No. 690 (2017) Obstet Gynecol 129 (3):e35-e40 (PMID: 28225425)
  4. Edwards et al. (2015) Obstetrics And Gynecology 125 (3):653-62 (PMID: 25730230)
  5. Gambin et al. (2015) Genome Med 7 (1):54 (PMID: 26195989)
  6. Ji et al.(2016) J Mol Diag. 18(3):438-445 (PMID: 26947514)
  7. Lazarou et al. (1998) JAMA 279 (15):1200-5 (PMID: 9555760)
  8. Linderman et al. (2016) J Pers Med 6 (2): (PMID: 27023617)
  9. Patiño et al. (2017) Hum. Reprod. 1-9 (PMID: 28505269)
  10. Plumpton et al. (2016) Pharmacoeconomics 34 (8):771-93 (PMID: 26984520)
  11. Qiao et al. (2016) Mol. Hum. Reprod. (PMID: 26826164)
  12. Qin et al. (2015) Hum. Reprod. Update 21 (6):787-808 (PMID: 26243799)
  13. Ray et al. (2017) Clin. Genet. 91 (2):217-232 (PMID: 27779748)
  14. Relling and Evans. (2015) Nature. 15:526(7573): 343-350 (PMID: 26469045)
  15. Retterer et al. (2016) Genet. Med. 18 (7):696-704 (PMID: 26633542)
  16. Richards et al. (2015) Genetics In Medicine 17 (5):405-24 (PMID: 25741868)
  17. Sallevelt et al. (2016) Genet. Med. : (PMID: 27787503)
  18. Spear et al. (2001) Trends Mol Med 7 (5):201-4 (PMID: 11325631)
  19. Tsurusaki et al. (2014) Clin. Genet. 85 (6):592-4 (PMID: 23826986)
  20. Van Driest et al. (2014) Clin Pharmacol Ther. 95(4): 423-431 (PMID: 24253661)

Clinical Genome Sequencing

GenomeSeqDx

Forms and Documents

Test Details

  • Determination of a clinical diagnosis
  • Identification of gene implicated in genetic disease
  • Recurrence risk assessment
  • Next-Gen Sequencing

Ordering

J774
16 weeks
2-5 mL Blood - Lavender Top Tube

Billing

81425, 81426x2
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Bamshad et al. (2011) Nature Reviews. Genetics 12 (11):745-55 (PMID: 21946919)
  2. Lelieveld et al. (2015) Hum. Mutat. 36 (8):815-22 (PMID: 25973577)
  3. Belkadi et al. (2015) Proc. Natl. Acad. Sci. U.S.A. 112 (17):5473-8 (PMID: 25827230)
  4. Retterer et al. (2016) Genet. Med. 18 (7):696-704 (PMID: 26633542)
  5. Richards et al. (2015) Genetics In Medicine 17 (5):405-24 (PMID: 25741868)

ReproXpanded

ReproXpanded Individual

Forms and Documents

Test Details

  • A previous pregnancy loss or deceased child for which there is no DNA available from the proband
  • Unexplained infertility
  • Multiple miscarriage of unknown etiology

ReproXpanded is a targeted test that uses whole exome capture, NextGeneration sequencing, and targeted analysis to assess for carrier status in all currently known disease genes. ReproXpanded can be used to assess reproductive risk in couples and individuals who have already completed standard carrier screening.

Each individual is analyzed individually and receives a ReproXpanded report. If both members of a couple are submitted simultaneously, both partners can also be analyzed for shared genetic risk.

  • Next-Gen Sequencing

Ordering

J776
10 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81415
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Amiri-Yekta et al. (2016) Hum. Reprod. 31 (12):2872-2880 (PMID: 27798045)
  2. Committee Opinion No. 690 (2017) Obstet Gynecol 129 (3):e35-e40 (PMID: 28225425)
  3. Edwards et al. (2015) Obstetrics And Gynecology 125 (3):653-62 (PMID: 25730230)
  4. Gambin et al. (2015) Genome Med 7 (1):54 (PMID: 26195989)
  5. Patiño et al. (2017) Hum. Reprod. 1-9 (PMID: 28505269)
  6. Qiao et al. (2016) Mol. Hum. Reprod. (PMID: 26826164)
  7. Qin et al. (2015) Hum. Reprod. Update 21 (6):787-808 (PMID: 26243799)
  8. Ray et al. (2017) Clin. Genet. 91 (2):217-232 (PMID: 27779748)
  9. Retterer et al. (2016) Genet. Med. 18 (7):696-704 (PMID: 26633542)
  10. Richards et al. (2015) Genetics In Medicine 17 (5):405-24 (PMID: 25741868)
  11. Sallevelt et al. (2016) Genet. Med. (PMID: 27787503)
  12. Tsurusaki et al. (2014) Clin. Genet. 85 (6):592-4 (PMID: 23826986)
  13. Yates et al. (2017) Genet. Med. (PMID: 28425981)
ReproXpanded Couple

Forms and Documents

Test Details

  • A previous pregnancy loss or deceased child for which there is no DNA available from the proband
  • Unexplained infertility
  • Multiple miscarriage of unknown etiology

ReproXpanded is a targeted test that uses whole exome capture, NextGeneration sequencing, and targeted analysis to assess for carrier status in all currently known disease genes. ReproXpanded can be used to assess reproductive risk in couples and individuals who have already completed standard carrier screening.

Each individual is analyzed individually and receives a ReproXpanded report. If both members of a couple are submitted simultaneously, both partners can also be analyzed for shared genetic risk.

  • Next-Gen Sequencing

Ordering

J842
10 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81415x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Amiri-Yekta et al. (2016) Hum. Reprod. 31 (12):2872-2880 (PMID: 27798045)
  2. Committee Opinion No. 690 (2017) Obstet Gynecol 129 (3):e35-e40 (PMID: 28225425)
  3. Edwards et al. (2015) Obstetrics And Gynecology 125 (3):653-62 (PMID: 25730230)
  4. Gambin et al. (2015) Genome Med 7 (1):54 (PMID: 26195989)
  5. Patiño et al. (2017) Hum. Reprod. 1-9 (PMID: 28505269)
  6. Qiao et al. (2016) Mol. Hum. Reprod. (PMID: 26826164)
  7. Qin et al. (2015) Hum. Reprod. Update 21 (6):787-808 (PMID: 26243799)
  8. Ray et al. (2017) Clin. Genet. 91 (2):217-232 (PMID: 27779748)
  9. Retterer et al. (2016) Genet. Med. 18 (7):696-704 (PMID: 26633542)
  10. Richards et al. (2015) Genetics In Medicine 17 (5):405-24 (PMID: 25741868)
  11. Sallevelt et al. (2016) Genet. Med. (PMID: 27787503)
  12. Tsurusaki et al. (2014) Clin. Genet. 85 (6):592-4 (PMID: 23826986)
  13. Yates et al. (2017) Genet. Med. (PMID: 28425981)

Special Services

Service Available Description More Information
Carrier/Mutation-specific testing GeneDx can provide Mutation-Specific Testing for known familial mutations, in any gene, for families that have had previous XomeDx or XomeDxPlus testing at GeneDx. Mutation-Specific Testing is offered for both symptomatic and asymptomatic individuals, and for dominant, recessive, or maternally inherited mutations. Mutation-Specific Testing is less costly and more rapid than diagnostic analysis of the whole gene. Pricing is dependent on whether testing is done for one or two mutations. For XomeDx mutation specific testing, please click here to fill out the XomeDx form.
Test Requisition
Release of Exome Aligned Sequence Data GeneDx is able to release whole exome sequence (WES) data for individuals who have undergone XomeDx, XomeDxPlus, XomeDxXpress, or XomeDxPrenatal testing. Data is available as CRAM (compressed BAM file) or VCF files with the signed consent of the patient and applicable family members. GeneDx has generated this sequence data using massively parallel (NextGen) sequencing to target exon regions. The targeted regions were sequenced on an Illumina sequencing system with 100bp or greater paired-end reads. GeneDx has evaluated the data generated by the XomeDx test for the purpose of a genetic diagnosis based on the reported clinical features. GeneDx does not provide interpretation or confirmation by an orthogonal test method for variants unrelated to the patient’s clinical features as indicated to GeneDx at the time of testing. Variants not included in the GeneDx report should be considered research results and should not be used for medical management without appropriate confirmation and interpretation by a qualified genetics provider.
-
XomeDx Data Release FAQs

 

FAQ

What is exome sequencing and when is it useful?

Exome sequencing targets the protein-coding regions, called exons, of the approximately 20,000 genes in the genome. It is a powerful diagnostic tool, providing a definitive diagnosis in 20-50% of patients (Yang, et al. N Engl J Med. 2013 Oct 17;369(16):1502-11, and GeneDx, Retterer et al., Genet Med. 2015 Dec 3). Exome sequencing can be used to identify the molecular basis of a genetic disorder in individuals:

  • With a genetically heterogeneous disease as pathogenic findings could be present in many different genes
  • With a long list of differential diagnoses
  • With an atypical presentation of a genetic disorder
  • Who have exhausted other currently available genetic testing options
  • Who have suspected tissue-specific mosaicism

What does GeneDx need to perform XomeDx testing?

  • Proband’s specimen. Please visit the Specimen Requirement Page for more information.
  • Family member samples, if appropriate depending on Xome test requested.
  • Completed XomeDx Test Requisition Form and signed Informed Consent Form.
  • Medical records, including prior test results, consult notes, and pedigree/family history. Client is encouraged to provide specific genes/disorders of interest and differential diagnosis.

What is the cost of XomeDx?

Questions regarding pricing and billing can be directed to GeneDx Customer Service at GeneDx@genedx.com or by calling 1-888-729-1206.

How long will it take to receive XomeDx results?

The turnaround time will vary depending on the specific Xome test requested. Please see the specific test page for additional information.

Whose specimens should be sent for XomeDx and what testing is performed?

When a trio (proband plus both parents) is sent for XomeDx and XomeDxPlus, exome sequencing is always performed on each member of the trio. This improves the sensitivity of the analysis when compared to testing only the proband. In some cases, including siblings or other relatives of the proband can be helpful. GeneDx will decide, in consultation with the ordering provider, which individuals will optimize our ability to identify a genetic cause of the patient’s features. We will also discuss the type of testing that is most useful and appropriate (i.e. exome sequencing or targeted variant testing to determine segregation). All individuals’ samples should be submitted at the beginning of testing. Relative samples may be collected and shipped separately from the proband sample; however, relative specimens must be received within three weeks of receipt of the proband's sample. In general, only a single report will be issued for the proband. However, the report will describe the inheritance and segregation of variants for all tested individuals.

Although exome sequence data may be generated on relatives, this data is only used to aid in the analysis of the proband's data. GeneDx does not conduct an independent analysis on relative samples. A second, independent analysis on a relative can be ordered, additional fees apply.

Can I send a different relative if a parent is unavailable?

Biological parents are typically the most informative samples and are accepted whenever possible. If parents are unavailable, other relatives may be considered on a case by case basis. To review details of a specific case, you can contact a GeneDx Clinical Genomics Genetic Counselor at GeneDx@genedx.com or 1-888-729-1206.

Is exome sequencing via a trio better than a proband alone?

The positive rate is highest when a trio is submitted/analyzed, as the inclusion of parental data improves the ability to classify variants. The absence of parental data may lead to over reporting of variants of unknown significance that could otherwise be dismissed based on inheritance patterns.

Can you use XomeDx to screen the parents for carrier status of recessive diseases?

Carrier testing for autosomal recessive conditions is best performed via other tests, such as ReproXpanded and/or GenPath: Inherigen.

How does GeneDx identify variants associated with the patient’s phenotype?

Exome sequencing will identify hundreds of thousands of variants. Variants are filtered using a variety of factors including population frequency, presence of gene and/or variant in HGMD or other databases, inheritance pattern, phenotype, severity of sequence change, and function in pathways. The clinical information provided by the ordering provider, including a description of the features, family history, and prior test results, is critical in the analysis of variants.

What will the test report include?

A single XomeDx report will be issued on the proband/main affected individual in the family. A separate report will not be issued for family members who may also have submitted a specimen for the purpose of allowing better interpretation of the results from the affected individual. If additional reports are requested for other affected family members, additional fees will apply. The XomeDx report issued for the affected individual will contain variations in genes previously implicated in a human disease similar to the affected individual or in genes hypothesized to be related to the cause of the disease (candidate genes), based upon the function, tissue of expression, and phenotype of model organisms with alterations in the gene. Variants in candidate genes may also be reported based on internal data, such as observations of previous XomeDx cases with similar phenotypes and types of variations in the same gene.

What are ACMG Secondary Findings?

The American College of Medical Genetics and Genomics (ACMG) recommends that secondary findings identified in a specific subset of genes associated with medically actionable, inherited disorders be reported for all probands undergoing exome sequencing, specifically when these variants are known and/or expected to be disease-causing.

Please refer to the latest version of the ACMG Recommendations for Reporting of Secondary Findings in Clinical Exome and Genome Sequencing Report for complete details of the genes and associated genetic disorders. If appropriate for the specific XomeDx test, secondary findings will be included in the test report, unless a proband opts-out of receiving this information in the Patient Consent portion of the XomeDx Test Requisition Form. The presence of any secondary finding(s) reported for the affected individual will be provided for all relatives tested by XomeDx or XomeDxPlus. GeneDx does not conduct an independent evaluation of secondary findings in relatives as part of the proband's XomeDx test. Relatives have the ability to opt-out of receiving secondary findings. Secondary findings will be confirmed by an alternate test method.

Can I request a separate report for family members that includes ACMG secondary findings not present in the proband?

Yes, as a separate test. An independent analysis for ACMG secondary findings can be ordered via XomeDxSlice, test code 706. ACMG secondary findings are also reported as part of XomeDxInsights, an exome based test designed for generally healthy adults who would like to learn about medically relevant changes in their genetic code, and their risk to have or develop certain genetic conditions.

Are there any findings that will NOT be reported?

A single report will be issued on the main affected individual in the family, referred to as the proband. No separate reports will be issued for the parents or other unaffected relatives. Variants known to be benign (not associated with any disease) and/or commonly seen in many other healthy people will not be reported. If a patient opts-out of receiving secondary findings, we will not analyze or report variants in the ACMG-recommended genes unless they are related to the patient’s phenotype. Only variants associated with the proband's reported clinical features will be reported and/or ACMG secondary findings if the family opted-in.

Will the analysis identify variants in disease-associated genes that are not associated with the patient’s reported phenotype?

Given the large number of genes analyzed via exome sequencing, pathogenic variants may be detected in genes that may be medically significant, but not associated with the primary reason for testing in a given patient.

In rare cases, GeneDx may report an incidental finding in a gene that is not one of the genes recommended by the ACMG. These reported findings must be pathogenic variants identified in the coding exons of genes, considered medically actionable, with the results expected to have a significant impact on the patient's health. These findings are not reported without prior discussion with the ordering clinician.

Are there genes that are not well covered by this method?

It is possible that entire genes may not be able to captured and sequenced in a particular patient, though in general we expect that there are only small portions of different genes not amenable to evaluation. Some exons have low or no coverage because no probes have been designed or are unavailable for these regions. It may be challenging to obtain usable sequence data for some regions. To check coverage of specific genes via exome sequencing, visit the XomeDxSlice Tool.

What sequencing platform and capture kit is GeneDx using?

GeneDx uses an Illumina sequencing platform and IDT xGen v1.0 capture.

What is the methodology?

Genomic DNA from the submitted specimen is enriched for the complete coding regions and splice site junctions for most genes of the human genome using a proprietary capture system developed by GeneDx for next-generation sequencing with CNV calling (NGS-CNV). The enriched targets are simultaneously sequenced with paired-end reads on an Illumina platform. Bi-directional sequence reads are assembled and aligned to reference sequences based on NCBI RefSeq transcripts and human genome build GRCh37/UCSC hg19. Using a custom developed analysis tool (XomeAnalyzer), data are filtered and analyzed to identify sequence variants and most deletions and duplications involving three or more coding exons (Retterer et al., 2015). Smaller deletions or duplications may not be reliably identified. Reported clinically significant variants are confirmed by an appropriate orthogonal method in the proband and, if submitted, in selected relatives as necessary. Reportable variants include pathogenic variants, likely pathogenic variants and variants of uncertain significance. Likely benign and benign variants, if present, are not routinely reported.

Can I get the capture target .bed file?

GeneDx exome sequencing uses IDT xGen v1.0 and the bed file for the probe and target locations are available directly from IDT: https://www.idtdna.com/pages/products/next-generation-sequencing/hybridization-capture/lockdown-panels/xgen-exome-research-panel (near the bottom of the page under Resources).

What are the statistics for coverage/quality?

Approximately 95% of the targeted region of an affected individual’s exome will be assessed with the XomeDx test at a minimum of 10x coverage, while >98% of the target region will be covered at a minimum of 1x. The test report will include patient-specific exome coverage.

Does exome sequencing detect copy number variants (i.e. deletions, duplications)?

Since 2014, GeneDx has been detecting copy number variants (CNVs) directly from exome sequencing data using an in-house developed algorithm (Retterer et al., 2015, PMID 25356966). This method can reliably detect most deletions and duplications involving three or more coding exons; smaller deletions or duplications may not be reliably identified. All reported CNVs are confirmed by an orthogonal method such as array CGH, MLPA, or PCR and parental confirmations for reportable CNVs are reported without additional charges. CNV analysis may not be possible in approximately 5% of samples. All Xome-based reports will include whether CNV detection was possible. At this time, exome based technology is not a replacement for the sensitivity of exon level aCGH.

Our CNV analysis via XomeDx can identify:

  • Large multi-gene chromosomal aberrations
  • Small, partial gene, and intragenic CNVs; deletions and duplications of three exons or larger are reliably identified
  • CNVs of one to two exons in size may be identified and comprise >50% of our previously reported exon-level variants
  • Chromosomal aneuploidy
  • Uniparental disomy, including isodisomy and heterodisomy
  • Inheritance of CNVs when a trio is submitted

CNV analysis is limited or may not be possible in regions with reduced coverage, extreme GC- or AT-content, or significant homology to pseudogenes or segmental duplications. Our method may not always detect: balanced aberrations, mosaicism, deletions/duplications involving only part of an exon, or CNVs in non-coding regions of the genome. For more information, Click Here.

My patient's test report was negative but I know a genetic condition is present in the family. What additional testing can be requested?

A negative report means we did not detect any variants related to the reported clinical features in any area of the exome that was tested at the time of the analysis. It certainly is possible that the cause of the affected individual’s disease is due to an underlying genetic condition. There could be a variant in a region of the exome that is not covered by this test, a type of variant that cannot be detected by the exome test, or there may be a variant that is observed in a gene not yet known to cause human disease. Depending on the specific situation and condition of interest in a given family, additional genetic testing may be warranted.

Reanalysis of the previously generated exome data can be considered, since technology and bioinformatics pipelines continuously improve and new disease genes are published.

What is reanalysis and when should I request this?

Reanalysis is the process of reexamining the sequencing data generated from the XomeDx test. This is most commonly requested when the initial exome sequencing did not yield a definitive result and may be especially helpful in cases where there are changes to the phenotype. Generally, reanalysis is recommended to occur at least one year after the date of the initial XomeDx report. Currently, we offer a one-time, no-charge reanalysis for every XomeDx or XomeDxPlus test.

What if extended family members want to be tested for a variant which was identified in a patient by XomeDx testing?

Family members can be tested for variants identified in the initial patient. If the variants detected in the proband are classified as pathogenic or likely pathogenic, family member testing can be ordered via Targeted Variant Testing (Site-Specific).

Laboratories classify genetic changes as variants of uncertain significance (VUS) if there is incomplete or conflicting information about the health consequences of the variant. In some cases, testing family members for the presence or absence of the VUS may contribute to a better understanding of the variant and may be one piece of evidence leading to eventual reclassification of a VUS as a pathogenic, likely pathogenic, benign, or likely benign variant. For such cases, GeneDx has established a Variant Testing Program (VTP). GeneDx considers requests for the Clinical Genomics VTP for any individual found to have a VUS in a disease-causing gene through exome or genome sequencing at our laboratory. These studies will be performed at no additional charge for select and pre-approved family members who meet certain criteria and for whom appropriate clinical information is provided. Genetic testing for other variants or additional family members, including predictive testing, is not included in our VTP and can be ordered separately for charge. GeneDx will make the final determinations for VTP in its sole discretion.

Inquiries regarding the Clinical Genomics VTP can be directed to GeneDx Clinical Genomics genetic counselors via email GeneDx@genedx.com, phone 301-519-2100, or fax 301-519-2892, that includes a detailed pedigree and any relevant clinical information/evaluations. Please be sure to indicate that you are submitting the information for VTP consideration, and include the name and/or GeneDx accession number of the proband.

I still have questions regarding an XomeDx test. Who should I contact?

You can contact a Clinical Genomics Genetic Counselor through our Customer Service team:

Secondary Findings

GeneDx will report out known or expected pathogenic variants in the genes recommended by the American College of Medical Genetics and Genomics (ACMG). GeneDx is currently evaluating probands for ACMG SF v2.0 (Kalia et al., 2016). The presence or absence of the proband’s identified secondary findings is available for relatives who underwent whole exome sequencing or targeted segregation analysis as part of the proband’s test. ACMG secondary findings are not reported for relatives that opted out of receiving ACMG secondary findings. Variants that may be present in a relative, but are not present in the proband, would not be detected and therefore are not reported. Only variants that have been previously reported and are a recognized cause of the disorder (known pathogenic; KP) or variants that are previously unreported but are of the type which is expected to cause the disorder (expected pathogenic; EP), as specified in the ACMG recommendations are reported (Kalia et al., 2016; Green et al., 2013; Richards et al., 2015). Known or expected pathogenic variants may be present in a portion of the gene not covered by XomeDx and therefore would not be detected. The absence of reportable secondary findings for any particular gene does not mean there are no known or expected pathogenic variants in that gene, or other variants that may confer susceptibility to the disorders listed.

A current list of genes and disorders for which findings may be reported can be found here.

Clinical Genomics (Exome and Genome Sequencing) Variant Testing Program (VTP)

Laboratories classify genetic changes as variants of uncertain significance (VUS) if there is incomplete or conflicting information about the health consequences of the variant. In some cases, testing family members for the presence or absence of the VUS may contribute to a better understanding of the variant and may be one piece of evidence leading to eventual reclassification of a VUS as a pathogenic, likely pathogenic, benign, or likely benign variant. For such cases, GeneDx has established a Variant Testing Program (VTP).

How do I determine if a variant is eligible for the Clinical Genomics VTP?

GeneDx considers requests for the Clinical Genomics VTP for any individual found to have a VUS in a disease-causing gene through exome or genome sequencing at our laboratory. These studies will be performed at no additional charge for select and pre-approved family members who meet certain criteria and for whom appropriate clinical information is provided. Genetic testing for other variants or additional family members, including predictive testing, is not included in our VTP and can be ordered separately for charge. GeneDx will make the final determinations for VTP in its sole discretion.

Application process for the Clinical Genomics VTP:

  • Please fax a detailed pedigree and any relevant clinical information/evaluations to the GeneDx Clinical Genomics genetic counselors at 301-519-2892, email genedx@genedx.com, or call 301-519-2100 and ask to speak with a Clinical Genomics genetic counselor. Please be sure to indicate that you are submitting the information for VTP consideration, and include the name and/or GeneDx accession number of the proband.
  • Our team will review the case and will determine if there are informative family members appropriate for evaluation through the VTP. Cases are typically reviewed within a few days, but please allow up to 3 weeks after receipt of the application for a reply.
  • A member of our team will contact the ordering clinician after the case has been reviewed to let him/her know if the family has been accepted in the VTP. If we are extending an offer for family member variant testing at no additional charge, we will discuss logistics of sample submission at that time.

Reasons why a family might not be accepted into the Clinical Genomics VTP:

  • The VUS is in a gene for which there is no currently described phenotype (i.e. candidate or novel gene).
  • There are no informative family members available for testing.
  • In certain circumstances, it may be more informative to perform more comprehensive diagnostic genetic testing in affected family member(s) instead of targeted testing of one or more unaffected relatives for a VUS.
  • Segregation studies involving genes with incomplete penetrance or variable age-of-onset are challenging, especially in unaffected individuals; therefore, VTP studies are less likely to be approved for such genes.
  • Segregation studies involving genes that may cause either an autosomal dominant or an autosomal recessive disorder are also more challenging than studies involving highly penetrant autosomal dominant genes; therefore, VTP studies are less likely to be approved for such genes.
  • Variant studies for the evaluation of a single VUS in a gene associated with an autosomal recessive disorder are rarely informative. Therefore, these requests are typically denied.

Revising the classification of variants of uncertain significance takes a great deal of data and information from multiple sources. Therefore, there is no guarantee that participation in the VTP will lead to an updated classification of a VUS based on information from a single family, although cumulative data collected from multiple families over time may lead to a more definitive classification for a variant.

For more information please contact:
The GeneDx Clinical Genomics genetic counselors at 301-519-2100