Pan Cardiomyopathy Panel (62 Genes)

Methodology

The Pan Cardiomyopathy Panel includes 62 genes: ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CASQ2, CAV3, CHRM2, CRYAB, CSRP3, DES, DMD, DOLK, DSC2, DSG2, DSP, DTNA, EMD, FHL2, GATAD1, GLA, ILK, JPH2, JUP, LAMA4 (excludes exon 2A* in NM_001105209.1 and exon 8 in NM_002290.3), LAMP2, LDB3, LMNA (excludes exons 1B* and 13B* in NM_001257374.2), CAVIN4, MYBPC3, MYH6 (excludes exon 37 in NM_002471.3), MYH7, MYL2, MYL3, MYLK2, MYOM1, MYOZ2, MYPN, NEBL, NEXN, PDLIM3, PKP2, PLN, PRDM16, PRKAG2, PTPN11, RAF1, RBM20, RYR2, SCN5A, SGCD, TAZ, TCAP, TMEM43, TNNC1, TNNI3, TNNT2, TPM1, TRDN, TTN, TTR, VCL. *Exon from an alternate transcript. For additional information on reference sequences and exon coverage, please visit our website (www.partners.org/personalizedmedicine/lmm). Genome sequence is generated from genomic DNA that is fragmented and barcoded followed by sequencing on the Illumina NovaSeq instrument with a minimum coverage of at least 20X for 95%. Reads are aligned to the NCBI reference sequence (GRCh38), using the Burrows-Wheeler Aligner (BWA), and variant calls are made using the Genomic Analysis Tool Kit (GATK). Technical sensitivity of this assay is 99.10% (95% CI: 99.04- 99.16%) and positive predictive value is 99.39% (95% CI: 99.37-99.41%). Detection of copy number variants (CNVs) encompassing 2 or more exons is performed using next-generation sequencing read data and the VisCap algorithm. CNV analysis is only performed when data meets necessary quality standards and may not be available for all cases. Variant calls are limited bioinformatically to the associated region of interest for the assay (see above for details). All clinically significant variants are confirmed by Sanger sequencing or droplet digital PCR; variants classified as likely benign or benign are not confirmed. Variant classifications are based on ACMG/AMP criteria (Richards et al. 2015) with ClinGen rule specifications (https://www.clinicalgenome.org/working-groups/sequence-variant-interpretation/). Variants are reported according to HGVS nomenclature (www.hgvs.org/mutnomen). Likely benign and benign variants are not included in this report but are available upon request. Specific types of genetic variation, such as triplet repeat expansions, structural variation, and copy number events are currently not reliably detected by this assay. Additionally, while genome sequencing covers ~95% of the genome; there are certain regions for which the assay may fail to adequately generate sequence information, such as regions of high homology. Variant interpretation may change over time if more information becomes available. This test was developed, and its performance characteristics determined by the Laboratory for Molecular Medicine at Partners HealthCare Personalized Medicine (LMM, 65 Landsdowne St, Cambridge, MA 02139; 617-768-8500; CLIA#22D1005307). It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary.

Citations

Not provided

All clinically significant variants are confirmed by Sanger sequencing or an alternate assay.