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LowBoneDensityZoom

Genes:
See test page
ALPL, ANKH, ANO5, ATP6V0A2, B4GALT7, BMP1, CASR, CLCN5, COL1A1, COL1A2, CREB3L1, CRTAP, CYP27B1, DMP1, ENPP1, FGF23, FKBP10, GNAS, GORAB, IFIH1, IFITM5, LMNA, LRP5, MAFB, MMP2, NOTCH2, P3H1, P4HB, PHEX, PLOD2, PLS3, PPIB, PTH1R, PYCR1, RUNX2, SEC24D, SERPINF1, SERPINH1, SLC34A3, SP7, SPARC, TMEM38B, TNFRSF11A, TNFRSF11B  , TREM2, TRPV6, TYROBP, WNT1, XYLT2, ZMPSTE24
 

Test Information

Test Method

DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

 

Clinical Utility

Discrimination between multiple heritable disorders associated with decreased bone mineral density; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier testing of relatives of proband and/or predictive prenatal testing.

Clinical Sensitivity

The detection rate for the LowBoneDensityZoom panel is undetermined at this point, due to ongoing research in the field.

 

Analytic Sensitivity

Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

 

Sample Requirements

3-6ml whole blood in EDTA (purple topped) tubes
Saliva collected in an appropriate collection device (Oragene®-DNA 500 or 600 device)
DNA extracted from fibroblast or lymphocyte cell line (must be extracted in a CLIA-certified laboratory)

 

Turn Around Time

6-8 weeks

Fee and CPT Codes

Exome Panel: $2915
CPT Code: 81479
*If you are a provider outside of Johns Hopkins we are only accepting institutional billing