Comprehensive Thyroid Genetic Testing for Precision Endocrinology

Overview

Thyroid disorders constitute a significant clinical and public health concern, impacting metabolic regulation, neuro development, cardiovascular health, and oncologic outcomes. While many thyroid pathologies are acquired, a substantial subset arises from germline genetic alterations that disrupt hormone biosynthesis, cellular signaling, and proliferative control. Early identification of these variants allows for improved diagnostic precision, therapeutic stratification, and long-term patient management.

PreCheck Health Services has developed a robust 59-geneComprehensive Thyroid Genetic Panel designed to elucidate the molecular basis of hereditary and sporadic thyroid diseases. This panel is clinically validated to detect single-nucleotide variants (SNVs) and small indels within critical coding and flanking intronic regions, enabling actionable insights across as pectrum of endocrine and oncologic presentations.

Clinical Significance

Genetic testing plays a transformative role in the management of thyroid disease. Inherited pathogenic variants can lead to congenital hypothyroidism, thyroid hormone resistance, thyroid dysgenesis, autoimmune predispositions, and neoplasia, including medullary and papillary thyroid carcinomas. Molecular diagnosis facilitates tailored treatment, risk-reducing interventions, and familial cascade testing.

Clinical indications for testing include:

- Neonatal or early-onset hypothyroidism or hyperthyroidism

- Unexplained thyroid hormone resistance syndromes

- Indeterminate or suspicious thyroid nodules on cytology(Bethesda III/IV)

- Personal or family history of differentiated or medullary thyroid carcinoma

- Suspected endocrine neoplasia syndromes or autoimmune polyglandular syndromes

Testing Panel Overview

This panel evaluates 59 genes selected based on evidence-based clinical utility, inclusion in professional guidelines, and relevance to thyroid hormone biosynthesis, organogenesis, oncogenesis, and immune regulation. The panel includes high-penetrance tumor suppressors, transcriptional regulators, membrane transporters, and hormone receptor components.

Technical Specifications

*Genes Covered: 59 clinically validated genes

*Analytical Sensitivity: >99% of targeted regions at>20x sequencing depth

*Turnaround Time: 10 to 14 calendar days

*Methodology: Targeted hybrid capture and high-throughput Illumina sequencing

*Variant Interpretation: Curated in accordance with ACMG/AMP guidelines using Fabric Enterprise™ Pipeline 6.6.15. Multidisciplinary review includes clinical geneticists and molecular pathologists.

*Reporting: Includes pathogenic and likely pathogenic variants with clinical annotations and management recommendations

Ideal Candidates for Testing

- Individuals with congenital hypothyroidism or abnormal neonatal screening

- Patients with refractory thyroid disorders or aberrant hormone profiles

- Subjects with a family history of thyroid cancer orMEN2-related syndromes

- Individuals undergoing evaluation for nodular thyroid disease with indeterminate FNA results

- Relatives of individuals with known thyroid-associated pathogenic variants

Clinical Utility and Impact

- Enhances diagnostic accuracy and clarifies ambiguous thyroid function profiles

- Facilitates personalized hormone replacement strategies

- Guides surgical decision-making in thyroid nodule and cancer management

- Enables risk-based surveillance and prophylactic measures for affected families

- Supports multidisciplinary care in complex endocrine-genetic syndromes

Conclusion

The integration of genetic testing into thyroid disease management has ushered in a new era of precision endocrinology. By enabling a deeper understanding of genetic contributions to thyroid function and pathology, PreCheck Health’s Comprehensive Thyroid Genetic Panel serves as a critical tool for personalized risk assessment, targeted intervention, and improved clinical outcomes. Clinicians are empowered to deliver informed care that anticipates disease progression, minimizes uncertainty, and supports proactive family-based medicine.

Test Methodology

The Thyroid Panel is designed to detect SNVs and small insertions/deletions in 59 genes relevant to thyroid pathology. The assay targets the coding exons and adjacent ±10 base pair intronic sequences. GenomicDNA is enriched using hybrid capture methods and sequenced using Illumina sequencing-by-synthesis (SBS) technology. Bioinformatics analysis is performed using the Fabric Enterprise™ Pipeline 6.6.15 with alignment to human genome build GRCh37. Variant classification follows ACMG/AMP criteria. Review and reporting are conducted by Fabric Clinical (CLIA ID: 45D2281059; CAP ID:9619501). Filters include: quality <500, allelic balance <0.3, coverage<10x.

Genes Evaluated

APC, CHEK2, DICER1, DUOX2, DUOXA2, FOXE1, GLIS3, GNAS,HESX1, IGSF1, IRS4, IYD, KDM6A, KMT2D, NKX2-1, NKX2-5, OTX2, PAX8, POU1F1,PRKAR1A, PROP1, PTEN, RET, SLC16A2, SLC26A4, SLC26A7, SLC5A5, TBL1X, TG, THRA,THRB, TP53, TPO, TRHR, TSHB, TSHR, UBR1, WRN, ATP1A2, CACNA1A, CST3, CSTB,CTNNB1, G6PD, GLIS3, HAMP, HFE, HRAS, KRAS, MECP2, NRAS, PIK3CA, PLCG2, PLN,SECISBP2, SLC40A1, TfR2, TGFBI, TTR

Test Limitations

This assay is limited to detection of SNVs and small indels in the targeted exonic and flanking intronic regions. It does not reliably detect large genomic deletions or duplications, structural variants, repeat expansions, mitochondrial mutations, or low-level mosaicism. Variants outside the targeted regions, including promoter/enhancer elements, may not be captured. Interpretation is based on the current state of scientific knowledge and may evolve with emerging evidence.

Regulatory Disclosures

This laboratory-developed test (LDT) was validated byPreCheck Health Services, Inc. and is performed in its CLIA-certified andCAP-accredited laboratory (CLIA ID: 10D2210020; CAP ID: 9101993). This assay has not been reviewed by the FDA, as approval is not required for LDTs used in certified laboratories for clinical diagnostics under CLIA.

For additional details, including full gene lists, ordering information, and support for interpretation, please contact our molecular diagnostics team at appointment@precheckhealth.com or visitwww.precheckhealth.com.

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