Diagnostic testing. CASR gene sequencing may be useful in the diagnostic workup of familial hypocalciuric hypercalcemia (FHH), autosomal dominant hypocalcemia, neonatal severe primary hyperparathyroidism (NSPHT), autosomal dominant hypoparathyroidism (ADH), Bartter syndrome, or kidney stones.

This assay will not consistently detect germline mosaicism below 50% or rule out the presence of large chromosomal aberrations, including rearrangements and inversions that do not change copy number of genomic regions. The assay does not detect repeat expansions. Possible intergenic variant interactions are not commented on. False positive or false negative results may occur for reasons that include: insufficient information available about rare genetic variants, sex chromosome abnormalities, pseudogene interference, homologous regions, blood transfusions, bone marrow transplantation, somatic or tissue-specific mosaicism, mislabeled samples, or erroneous representation of family relationships. Variants that do not alter an amino acid composition of a protein may be difficult to assess for pathogenicity since they may produce abnormalities in structures not assessed by conventional analysis paradigms, eg, mRNA expression and processing.1 For mitochondrial DNA variants, low levels of heteroplasmy (<1%) may not be reliably detected by this technique. Mitochondrial variants may be tissue-specific. Interpretation of the clinical significance of gene variations is limited by information about the variant that is available at the time of reporting, and by the quality and quantity of clinical information provided with the sample. As the understanding of human genetic diversity improves, the interpretation of the clinical significance of variants may change.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.