The PanCardiomyopathy 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 (includes deep intronic c.639+919G>A variant), 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 (includes the intronic c.1224-52G>A variant), 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 email LMM@partners.org
This assay is performed using Genomic DNA extracted from blood or saliva that is fragmented, adapter ligated, and barcoded. Library fragments are sequenced (2x150 base paired end) using Sequencing-By-Synthesis (SBS) chemistry and the Illumina NovaSeq sequencer with a minimum coverage of at least 20X for 90%. Sequence data are aligned to the GRCh38 assembly after discarding low quality sequences. Illumina's DRAGEN (Dynamic Read Analysis for GENomics) platform is used for demultiplexing, read mapping, genome alignment, read sorting, duplicate marking, and variant calling. Technical sensitivity of this assay is 99.10% (95% CI: 99.04-99.16%) and the positive predictive value is 99.39% (95% CI: 99.37-99.41%). Sanger sequencing is used for fill-in when bases have <12x coverage. 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. Variants are reported according to HGVS nomenclature. Likely benign and benign variants are not included in this report but are available upon request.
This test does not routinely detect variants in non-coding regions (aside from the canonical splice sites), triplet repeat expansions, translocations, inversions, and copy number variants. There is reduced detection for larger indels, variants in low complexity regions, and variants in regions with high homology.
The initial sequencing component of this test is performed by the Broad Clinical Laboratory of the Broad Institute (320 Charles St, Cambridge, MA 02141; CLIA#22D2055652), and the Sanger confirmation, interpretive algorithms and clinical reports are generated by the Laboratory for Molecular Medicine at Mass General Brigham Personalized Medicine (LMM, 65 Landsdowne St, Cambridge, MA 02139; 617-768-8500; CLIA#22D1005307). This test 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.
