Skip to main content
HealthPartners

Coverage criteria policies

Genetic Testing: Connective Tissue, Skeletal, and Integumentary Disorders

These services may or may not be covered by your HealthPartners plan. Please see your plan documents for your specific coverage information. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage.

Administrative Process

Prior authorization is required for genetic testing for connective tissue, skeletal, and integumentary disorders, except for the following services:

  • Cytogenetic and/or cytogenomic studies when associated with procedure codes from Code Table 1 below (under Codes)
  • HLA-B27 genotyping related to ankylosing spondylitis or nonradiographic axial spondyloarthritis when associated with procedure and primary diagnosis codes from Code Table 2 below (under Codes)

The scope of this coverage policy includes, but is not limited to, the following services:

  • Section 1: Cytogenetic and Cytogenomic Studies
  • Section 2: Human Leukocyte Antigen (HLA) Genotyping
  • Section 3: Genetic Testing for Ehlers-Danlos Syndrome
  • Section 4: Genetic Testing for Other Specified Connective Tissue, Skeletal, and Integumentary Disorders
  • Section 5: Exome Sequencing

For genetic testing related to reproductive planning, see the Genetic Testing: Carrier Screening, Prenatal Screening, Prenatal Diagnosis, and Infertility Evaluation coverage policy.

For genetic testing for multiple congenital anomalies, see the Genetic Testing: Neurological, Neurodevelopmental, and Sensory Disorders and Multiple Congenital Anomalies coverage policy.

Genetic testing for connective tissue, skeletal, and integumentary disorders other than as described below is subject to a review for medical necessity, based on current clinical literature and expert recommendations, unless listed as an indication that is not covered.

Coverage

Indications that are covered

Section 1: Cytogenetic and Cytogenomic Studies

Cytogenetic and cytogenomic studies (e.g., array comparative genomic hybridization [CGH], fluorescence in situ hybridization [FISH], karyotyping/chromosomal analysis/chromosomal banding) for connective tissue, skeletal, and integumentary disorders, are covered.

Section 2: Human Leukocyte Antigen (HLA) Genotyping

HLA-B27 genotyping related to ankylosing spondylitis or nonradiographic axial spondyloarthritis is covered.

Section 3: Genetic Testing for Ehlers-Danlos Syndrome

Single-gene analysis of the COL3A1 gene for Ehlers-Danlos syndrome (EDS), vascular type, is covered when criteria 1-4 listed below are met:

  1. The test is ordered by a licensed genetic counselor or a board-certified physician or advanced practice registered nurse in cardiology, dermatology, endocrinology, neurology, rheumatology, or medical genetics.
  2. The test is expected to directly impact management of the condition under evaluation.
  3. The member has received genetic counseling with a board-certified genetic counselor, medical geneticist, or advanced practice registered nurse in medical genetics who is not affiliated with the commercial testing laboratory, if applicable.
  4. The test has been recommended for one of the following indications:
    1. The member has a personal history consistent with the condition under evaluation
    2. The member has a first- or second-degree blood relative diagnosed with the condition under evaluation and a board-certified genetic counselor, medical geneticist, or advanced practice registered nurse in medical genetics certifies that the member is at risk for this condition.

Single-gene analysis (other than the COL3A1 gene) and multiple-gene analysis for Ehlers-Danlos syndrome are covered when criteria 1-4 listed below are met:

  1. The test is ordered by a licensed genetic counselor or a board-certified physician or advanced practice registered nurse in medical genetics.
  2. The test is expected to directly impact management of the condition under evaluation.
  3. The member has received genetic counseling with a board-certified genetic counselor, medical geneticist, or advanced practice registered nurse in medical genetics who is not affiliated with the commercial testing laboratory, if applicable.
  4. The test has been recommended for one of the following indications:
    1. The member has a personal history consistent with the condition under evaluation.
    2. The member has a first- or second-degree blood relative diagnosed with the condition under evaluation and a board-certified genetic counselor, medical geneticist, or advanced practice registered nurse in medical genetics certifies that the member is at risk for this condition.

Section 4: Genetic Testing for Other Specified Connective Tissue, Skeletal, and Integumentary Disorders

Single-gene analysis, multiple-gene analysis, and molecular expression profiling for the following conditions is covered when criteria 1-4 listed below are met:

  • Dentinogenesis imperfecta
  • Epidermolysis bullosa
  • Hereditary hemorrhagic telangiectasia
  • Hereditary hypophosphatemic rickets
  • Hypophosphatasia
  • Keratinopathic ichthyosis
  • Kindler syndrome
  • Legius syndrome
  • Loeys-Dietz syndrome
  • Marfan syndrome
  • Netherton syndrome
  • Neurofibromatosis, types 1 and 2
  • Osteogenesis imperfecta
  • Primary lymphedema
  • Recessive x-linked ichthyosis
  • Schwannomatosis
  • Tuberous sclerosis complex
  • Thoracic Aortic Aneurysm and Dissection (TAAD)
  1. The test is ordered by one of the specialists listed below, as applicable to the condition under evaluation:
    1. Primary lymphedema: A licensed genetic counselor or a board-certified physician or advanced practice registered nurse in medical genetics
    2. All other conditions listed above: A licensed genetic counselor or a board-certified physician or advanced practice registered nurse in cardiology, dermatology, endocrinology, neurology, rheumatology, or medical genetics
  2. The test is expected to directly impact management of the condition under evaluation.
  3. The member has received genetic counseling with a board-certified genetic counselor, medical geneticist, or advanced practice registered nurse in medical genetics who is not affiliated with the commercial testing laboratory, if applicable.
  4. The test has been recommended for one of the following indications:
    1. The member has a personal history consistent with the condition under evaluation.
    2. The member has a first- or second-degree blood relative diagnosed with the condition under evaluation and a board-certified genetic counselor, medical geneticist, or advanced practice registered nurse in medical genetics certifies that the member is at risk for this condition.

Section 5: Exome Sequencing

Whole exome sequencing, including comparator exome sequence analysis, is covered when criteria 1-4 below are met:

  1. The test is ordered by a licensed genetic counselor or a board-certified physician or advanced practice registered nurse in medical genetics.
  2. The test is intended for identification of a connective tissue, skeletal, or integumentary disorder that has not been successfully identified through previous genetic, cytogenomic, and/or cytogenetic analysis.
  3. The member has received genetic counseling with a board-certified genetic counselor, medical geneticist, or advanced practice registered nurse in medical genetics who is not affiliated with the commercial testing laboratory, if applicable.
  4. The member to be tested has documented features, characteristics, or symptoms consistent with a connective tissue, skeletal, or integumentary disorder of probable genetic etiology.

Indications that are not covered

  1. Genetic testing is not covered and is considered not medically necessary when test results will not directly impact the treatment or management of a condition or provide a unifying diagnosis for a previously unidentified condition because the testing is not expected to restore or maintain the member’s health, prevent deterioration of the member’s condition, nor prevent the reasonably likely onset of a health problem or detect an incipient problem.
  2. The following services are not covered and are considered not medically necessary because they are not within the practice parameters of the general medical community:
    1. Comparative analysis using short tandem repeat (STR) markers, which is considered integral to the primary procedure and ineligible for separate coverage
    2. Direct-to-consumer genetic testing
    3. Genetic testing for acquired disorders (those of non-genetic etiology, such as a condition caused by an identified environmental factor).
    4. Genetic testing which was not ordered by a licensed healthcare provider or physician (see Definitions) who has established a direct patient care relationship with the member to be tested.
    5. Genetic testing that is provided solely to satisfy data collection and analysis needs and that will not be used in direct clinical management.
    6. Predictive genetic testing for asymptomatic members under 18 years of age for conditions generally accepted as having an onset in adulthood.
  3. Repeat testing of a unique analyte using the identical method of analysis is not covered and is considered not medically necessary because it is not considered an appropriate frequency of care.
  4. Multiple-gene panels which include genes not associated with the specific condition, features, characteristics, or symptoms under evaluation, or including genes not associated with conditions within the ordering provider’s differential diagnosis list for the affected member, are not covered and are considered not medically necessary because they are not considered an appropriate type of service for the member’s condition.
  5. The following services are considered experimental/investigational because reliable evidence does not permit conclusions concerning safety, effectiveness, or effect on health outcomes:
    1. Genetic testing for the following indications:
      1. Familial partial lipodystrophy
      2. Idiopathic adolescent scoliosis
      3. Isolated abdominal aortic aneurysm
      4. Isolated mitral valve prolapse
      5. Hereditary multiple osteochondromas
      6. Homocystinuria
      7. Osteoporosis
      8. Peripheral pulmonary stenosis
      9. Pseudoxanthoma elasticum
    2. Whole genome sequencing

Definitions

First-degree relative is an individual’s parent, sibling, or child.

Healthcare provider is any licensed non-physician (excluding naturopathic providers).

Physician is a licensed medical doctor or doctor of osteopathy.

Second-degree relative is an individual’s grandparent, grandchild, aunt, uncle, nephew, niece, or half-sibling.

If available, codes are listed below for informational purposes only, and do not guarantee member coverage or provider reimbursement. The list may not be all-inclusive.

The services listed in Code Table 1 do not require prior authorization when associated with genetic testing for connective tissue, skeletal, or integumentary disorders.

Code Table 1

Codes

Description

81228

Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (eg, bacterial artificial chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis)

81229

Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities

88245

Chromosome analysis for breakage syndrome; baseline Sister Chromatic Exchange (SCE), 20-25 cells

88248

Chromosome analysis for breakage syndromes; baseline breakage, score 50-100 cells, count 20 cells, 2 karyotypes (eg, for ataxia telangiectasia, Fanconi anemia, fragile X)

88249

Chromosome analysis for breakage syndromes; score 100 cells, clastogen stress (eg, diepoxybutane, mitomycin C, ionizing radiation, UV radiation

88261

Chromosome analysis; count 5 cells, 1 karyotype, with banding

88262

Chromosome analysis; count 15-20 cells, 2 karyotypes, with banding

88263

Chromosome analysis; count 45 cells for mosaicism, 2 karyotypes, with banding

88264

Chromosome analysis, analyze 20-25 cells

88271

Molecular cytogenetics; DNA probe, each (eg, FISH)

88272

Molecular cytogenetics; chromosomal in situ hybridization, analyze 3-5 cells (eg, for derivatives and markers)

88273

Molecular cytogenetics; chromosomal in situ hybridization, analyze 10-30 cells (eg, for microdeletions)

88274

Molecular cytogenetics; interphase in situ hybridization, analyze 25-99 cells

88275

Molecular cytogenetics; interphase in situ hybridization, analyze 100-300 cells

88280

Chromosome analysis; additional karyotypes, each study

88283

Chromosome analysis; additional specialized banding technique (eg, NOR, C-banding)

88285

Chromosome analysis; additional cells counted, each study

88289

Chromosome analysis; additional high resolution study

The services listed in Column A of Code Table 2 do not require prior authorization when associated with any of the primary diagnoses listed in Column B of Code Table 2.

Code Table 2

Service (Column A)

Primary Diagnosis (Column B)

81370

HLA Class I and II typing, low resolution (eg, antigen equivalents); HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1

M08.1

Juvenile ankylosing spondylitis

M46.80

Other specified inflammatory spondylopathies, site unspecified

81371

HLA Class I and II typing, low resolution (eg, antigen equivalents); HLA-A, -B, and -DRB1 (eg, verification typing)

M45.0

Ankylosing spondylitis of multiple sites in spine

M46.81

Other specified inflammatory spondylopathies, occipito-atlanto-axial region

81372

HLA Class I typing, low resolution (eg, antigen equivalents); complete (ie, HLA-A, -B, and -C)

M45.1

Ankylosing spondylitis of occipito-atlanto-axial region

M46.82

Other specified inflammatory spondylopathies, cervical region

81373

HLA Class I typing, low resolution (eg, antigen equivalents); one locus (eg, HLA-A, -B, or -C), each

M45.2

Ankylosing spondylitis of cervical region

M46.83

Other specified inflammatory spondylopathies, cervicothoracic region

81374

HLA Class I typing, low resolution (eg, antigen equivalents); one antigen equivalent (eg, B*27), each

M45.3

Ankylosing spondylitis of cervicothoracic region

M46.84

Other specified inflammatory spondylopathies, thoracic region

81375

HLA Class II typing, low resolution (eg, antigen equivalents); HLA-DRB1/3/4/5 and -DQB1

M45.4

Ankylosing spondylitis of thoracic region

M46.85

Other specified inflammatory spondylopathies, thoracolumbar region

81376

HLA Class II typing, low resolution (eg, antigen equivalents); one locus (eg, HLA-DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, or -DPA1), each

M45.5

Ankylosing spondylitis of thoracolumbar region

M46.86

Other specified inflammatory spondylopathies, lumbar region

81377

HLA Class II typing, low resolution (eg, antigen equivalents); one antigen equivalent, each

M45.6

Ankylosing spondylitis lumbar region

M46.87

Other specified inflammatory spondylopathies, lumbosacral region

81378

HLA Class I and II typing, high resolution (ie, alleles or allele groups), HLA-A, -B, -C, and -DRB1

M45.7

Ankylosing spondylitis of lumbosacral region

M46.88

Other specified inflammatory spondylopathies, sacral and sacrococcygeal region

81379

HLA Class I typing, high resolution (ie, alleles or allele groups); complete (ie, HLA-A, -B, and -C)

M45.8

Ankylosing spondylitis sacral and sacrococcygeal region

M46.89

Other specified inflammatory spondylopathies, multiple sites in spine

81380

HLA Class I typing, high resolution (ie, alleles or allele groups); one locus (eg, HLA-A, -B, or -C), each

M45.9

Ankylosing spondylitis of unspecified sites in spine

   

81381

HLA Class I typing, high resolution (ie, alleles or allele groups); one allele or allele group (eg, B*57:01P), each

       

81382

HLA Class II typing, high resolution (ie, alleles or allele groups); one locus (eg, HLA-DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, or -DPA1), each

       

81383

HLA Class II typing, high resolution (ie, alleles or allele groups); one allele or allele group (eg, HLA-DQB1*06:02P), each

       

The services listed in Code Table 3 require prior authorization when associated with genetic testing for connective tissue, skeletal, or integumentary disorders.

Code Table 3

Code

Description

0004M

Scoliosis, DNA analysis of 53 single nucleotide polymorphisms (SNPs), using saliva, prognostic algorithm reported as a risk score

0012U

Germline disorders, gene rearrangement detection by whole genome next-generation sequencing, DNA, whole blood, report of specific gene rearrangement(s)

81400

MOLECULAR PATHOLOGY PROCEDURE LEVEL 1

81401

MOLECULAR PATHOLOGY PROCEDURE LEVEL 2

81402

MOLECULAR PATHOLOGY PROCEDURE LEVEL 3

81403

MOLECULAR PATHOLOGY PROCEDURE LEVEL 4

81404

MOLECULAR PATHOLOGY PROCEDURE LEVEL 5

81405

MOLECULAR PATHOLOGY PROCEDURE LEVEL 6

81406

MOLECULAR PATHOLOGY PROCEDURE LEVEL 7

81407

MOLECULAR PATHOLOGY PROCEDURE LEVEL 8

81408

MOLECULAR PATHOLOGY PROCEDURE LEVEL 9

81410

Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); genomic sequence analysis panel, must include sequencing of at least 9 genes, including FBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK

81411

Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); duplication/deletion analysis panel, must include analyses for TGFBR1, TGFBR2, MYH11, and COL3A1

81415

Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis

81416

Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator exome (eg, parents, siblings) (List separately in addition to code for primary procedure)

81417

Exome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained exome sequence (eg, updated knowledge or unrelated condition/syndrome)

81425

Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis

81426

Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator genome (eg, parents, siblings) (List separately in addition to code for primary procedure)

81427

Genome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained genome sequence (eg, updated knowledge or unrelated condition/syndrome)

81479

Unlisted molecular pathology procedure

CPT Copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association

Products

This information is for most, but not all, HealthPartners plans. Please read your plan documents to see if your plan has limits or will not cover some items. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage. These coverage criteria may not apply to Medicare Products if Medicare requires different coverage. For more information regarding Medicare coverage criteria or for a copy of a Medicare coverage policy, contact Member Services at 952-883-7979 or 1-800-233-9645.

References

  1. Beary, J. F., & Chines, A. A. (2018). Osteogenesis imperfecta: Clinical features and diagnosis. In: H. F. Firth & E. TePas (Eds.). UpToDate. Waltham, MA: UpToDate.
  2. Bruckner, A. L., & Murrell, D. F. (2018). Diagnosis of epidermolysis bullosa. In: J. L. Hand & R. Corona (Eds.). UpToDate. Waltham, MA: UpToDate.
  3. Choate, K. (2017). Keratinopathic ichthyoses. In: J. L. Hand, & R. Corona (Eds.). UpToDate. Waltham, MA: UpToDate.
  4. Dyer, J. A. (2018). Netherton syndrome. In: M. L. Levy, J. L. Hand, & R. Corona (Eds.). UpToDate. Waltham, MA: UpToDate.
  5. Evans, D. G. (2018). Neurofibromatosis type 2. In: J. S. Loeffler, P. Y. Wen, & A. F. Eichler (Eds.). UpToDate. Waltham, MA: UpToDate.
  6. Hand, J. L. (2017). Recessive x-linked ichthyosis. In: M. L. Levy & R. Corona (Eds.). UpToDate. Waltham, MA: UpToDate.
  7. Has, C. (2018). Kindler syndrome. In: J. L. Hand & R. Corona (Eds.). UpToDate. Waltham, MA: UpToDate.
  8. Hayes, Inc. (2015). Ehlers-Danlos syndrome (EDS), classic type. Philadelphia, PA: Hayes, Inc.
  9. Hiratzka, L. F., Bakris, G. L., Beckman, J. A., Bersin, R. M., Carr, V. F., Casey, D. E., . . . Williams, D. M. (2010). 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation, 121, e266-e369.
  10. Keels, M. A., & Tatakis, D. N. (2018). Periodontal disease in children: Associated systemic conditions. In: A. Griffen & M. M. Torchia (Eds.). UpToDate. Waltham, MA: UpToDate.
  11. Korf, B. R. (2018). Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis. In: M. C. Patterson, H. V. Firth, & E. TePas (Eds.). UpToDate. Waltham, MA: UpToDate.
  12. Mehrara, B. (2018). Clinical features and diagnosis of peripheral lymphedema. In: J. F. Eidt, J. L. Mills, H. Burstein, & K. A. Collins (Eds.). UpToDate. Waltham, MA: UpToDate.
  13. Miner, G. H., Faries, P. L., Costa, K. D., Hanss, B. G., & Marin, M. L. (2015). An update on the etiology of abdominal aortic aneurysms: Implications for future diagnostic testing. Expert Review of Cardiovascular Therapy, 13, 1079-1090.
  14. Pauker, S. P., & Stoler, J. (2018). Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. In: H. V. Firth & P. L. Roman (Eds.). UpToDate. Waltham, MA: UpToDate.
  15. Pislaru, S., & Enriquez-Sarano, M. (2017). Definition and diagnosis of mitral valve prolapse. In: C. M. Otto & S. B. Yeon (Eds.). UpToDate. Waltham, MA: UpToDate.
  16. Randle, S. (2017).Tuberous sclerosis complex: Genetics, clinical features, and diagnosis. In: H. V. Firth, A. S. Pappo, M. C. Patterson, & J. F. Dashe (Eds.). UpToDate. Waltham, MA: UpToDate.
  17. Ringold, S. (2018). Spondyloarthritis in children. In: M. Klein-Gitelman & E. TePas (Eds.). UpToDate. Waltham, MA: UpToDate.
  18. Scheinman, S. J., & Drezner, M. K. (2017). Hereditary hypophosphatemic rickets and tumor-induced osteomalacia. In: R. H. Sterns, M. E. Geffner, & A. G. Hoppin (Eds.). UpToDate. Waltham, MA: UpToDate.
  19. Scherl, S. A. (2018). Adolescent idiopathic scoliosis: Management and prognosis. In: W. Phillips & M. M. Torchia (Eds.). UpToDate. Waltham, MA: UpToDate.
  20. Shovlin, C. (2018). Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome). In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
  21. Tis, J. E. (2018). Benign bone tumors in children and adolescents. In: W. Phillips & M. M. Torchia (Eds.). UpToDate. Waltham, MA: UpToDate.
  22. Wooderchak-Donahue, W., VanSant-Webb, C., Tvrdik, T., Plant, P., Lewis, T., Stocks, J., . . . Bayrak-Toydemir, P. (2015). Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy. American Journal of Medical Genetics Part A, 167A, 1747-1757.
  23. Wright, M. J., & Connolly, H. M. (2016). Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders. In: H. C. Dietz & S. B. Yeon (Eds.). UpToDate. Waltham, MA: UpToDate.
  24. Wright, T. S. (2018). The genodermatoses. In: H. V. Firth, J. L. Hand, & R. Corona (Eds.). UpToDate. Waltham, MA: UpToDate.
  25. Yu, D. T., & Van Tubergen, A. (2018). Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults. In: J. Sieper & P. L. Romain (Eds.). UpToDate. Waltham, MA: UpToDate.
  26. Zarate, Y. A., Sellars, E., Lepard, T., Tang, X., & Collins, R. T. (2016). Aortic dilation, genetic testing, and associated diagnoses. Genetics in Medicine, 18, 356-363.

Go to

Policy activity

  • 06/21/2016 - Date of origin
  • 11/01/2018 - Effective date
Review date
  • 06/2018
Revision date
  • 08/10/2018

Related content