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Hypothyroidism [Congenital, Nongoitrous] and Hyperthyroidism [Familial Gestational and Nonautoimmune] via the TSHR 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
TSHR 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11779TSHR81479 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


  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Hypothyroidism is a condition wherein thyroid hormone production is not stimulated due to improperly functioning receptors. Impaired thyroid stimulating hormone (TSH) receptors may also disrupt thyroid development, and as a result, the gland is smaller than normal. TSH resistance is a disease with a broad range of expressivity going from severe congenital hypothyroidism (CH) with thyroid hypoplasia to mild hyperthyrotropinemia (hyperTSH) associated with an apparent euthyroid state (Persani et al. 2010).

Hyperthyroidism is caused when the thyroid gland is overactive, resulting in increased production of thyroid hormones. Clinical manifestations include an enlarged thyroid gland and increased heart beat (Hebrant et al. 2010). The presence of hyperthyroidism at birth is called nonautoimmune congenital hyperthyroidism (CH) or sporadic toxic thyroid hyperplasia, whereas onset in childhood or adulthood is known as nonautoimmune hyperthyroidism (or hereditary toxic thyroid hyperplasia). Hyperthyroidism is also seen in Graves Disease which is a common autoimmune thyroid disease associated with hyperthyroidism and goiter along with a wide range of other symptoms that can include anxiety, restlessness, and protruding eyes that may be red and swollen (Menconi et al. 2014).


Causative mutations in TSHR can be inherited as autosomal dominant or recessive (Trülzsch et al. 1999). Congenital hypothyroidism including nongoitrous, congenital hypothyridism is caused by inactivating mutations involved in autosomal dominant (Calebiro 2005) or autosomal recessive (Sunthornthepvarakul et al. 1995; Abramowicz et al. 1997) inherited TSH resistance. Genetic hyperthyroidism includes toxic thyroid nodules (due to constitutively activating somatic mutations) and sporadic congenital nonautoimmune hyperthyroidism and autosomal dominant familial nonautoimmune hyperthyroidism which occur due to constitutively activating germline mutations.

Hypo- and Hyperthyroidism associated with mutations in the thyroid stimulating hormone receptor (TSHR) gene, are caused by dysfunction of its protein product. TSHR codes for a cellular membrane receptor which spans the cells of the thyroid gland and serves as a customized binding site for the thyroid stimulating hormone (TSH). TSH is made in the pituitary gland and travels through the bloodstream to the thyroid gland. The hormone binds to the extracellular portion of the receptor, activating a series of reactions that control development of the thyroid gland and its functions. Among its functions, the thyroid gland produces iodine-containing hormones (thyroid hormones), which help regulate growth, brain development and metabolism (Mansourian 2011).

Congenital hypothyroidism is detected at a rate of 1 in 3000-4000 newborns, making it the most common congenital endocrine disorder, 80-85% of cases of which are due to thyroid gland dysgenesis (Park 2005). Thyroid dysgenesis is normally sporadic disease, but in about 5% of the cases a genetic origin has been demonstrated due to mutations in genes playing a role during thyroid morphogenesis such as NKX2-1, PAX8, FOXE1, NKX2-5 and TSHR (Nettore et al. 2013). The exact prevalence of familial hyperthyroidism on the other hand is not known, but it is expected to be rare, with TSHR causative mutations is believed to be between 1 in 23 to 1 in 172 (Persani et al. 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

TSHR is the only gene currently thought to be associated with genetic hyperthyroidism including sporadic congenital nonautoimmune hyperthyroidism and familial nonautoimmune hyperthyroidism. Though congenital hypothyroidism is associated with mutations in multiple genes, TSHR, PAX8, TSHB, NKX2-5 and THRA, mutations in TSHR are believed to be the most frequent cause with about 60 causative mutations identified so far (Persani et al. 2010).

Testing Strategy

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

Individuals with the following should be considered for testing for mutations in the TSHR gene (Cassio et al. 2012): elevated TSH levels persistently above or fluctuating around the upper limit of the normal range, decreased or near normal thyroid hormone (T3 and T4) levels, absence of anti-thyroid antibodies, normal or hypoplastic thyroid gland on ultrasound, and/or family history of thyroid disease. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TSHR.


Official Gene Symbol OMIM ID
TSHR 603372
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Abramowicz MJ, Duprez L, Parma J, Vassart G, Heinrichs C. 1997. Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J. Clin. Invest. 99: 3018–3024. PubMed ID: 9185526
  • Calebiro D. 2005. Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. Human Molecular Genetics 14: 2991–3002. PubMed ID: 16135555
  • Cassio A, Nicoletti A, Rizzello A, Zazzetta E, Bal M, Baldazzi L. 2012. Current loss-of-function mutations in the thyrotropin receptor gene: when to investigate, clinical effects, and treatment. Journal of Clinical Research in Pediatric Endocrinology 4: PubMed ID: 23154162
  • Hebrant A, Staveren WCG van, Maenhaut C, Dumont JE, Leclere J. 2010. Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations. European Journal of Endocrinology 164: 1–9. PubMed ID: 20926595
  • Mansourian, Azad Reza 2011Central Dogma in Thyroid Dysfunction: A Review on Structure Modification of TSHR as a Cornerstone for Thyroid Abnormalities. Pakistan Journal of Biological Sciences: PJBS 14(3): 170–181. PubMed ID: 21870640
  • Menconi F, Marcocci C, Marinò M. 2014. Diagnosis and Classification of Graves’ Disease. Autoimmunity Reviews 13(4-5): 398–402. PubMed ID: 24424182
  • Nettore, I C, V Cacace, C De Fusco, A Colao, and P E Macchia 2013The Molecular Causes of Thyroid Dysgenesis: A Systematic Review. Journal of Endocrinological Investigation 36(8): 654–664. PubMed ID: 23698639
  • Park SM. 2005. Genetics of congenital hypothyroidism. Journal of Medical Genetics 42: 379–389. PubMed ID: 15863666
  • Persani L, Calebiro D, Cordella D, Weber G, Gelmini G, Libri D, Filippis T de, Bonomi M. 2010. Genetics and phenomics of hypothyroidism due to TSH resistance. Mol. Cell. Endocrinol. 322: 72–82. PubMed ID: 20083154
  • Sunthornthepvarakul T, Gottschalk ME, Hayashi Y, Refetoff S. 1995. Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. New England Journal of Medicine 332: 155–160. PubMed ID: 7528344
  • Trülzsch B, Nebel T, Paschke R. 1999. The thyrotropin receptor mutation database. Thyroid 9: 521–522. PubMed ID: 10411112


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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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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