Laboratory for Molecular Medicine: Tests for Cardiomyopathy
Email: LMM@partners.org
Call: 617-768-8500
What we offer
Included with our list of offered genetic testing is supporting documentation as well as individual details specific to ordering of a particular test.
Inherited cardiomyopathies are a group of genetically heterogeneous cardiac diseases with a relatively high population frequency, association with sudden cardiac death, and substantial genetic component. Familial inheritance is common and typically follows an autosomal dominant pattern, though all other forms of inheritance exist. The predominant forms are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), followed by arrhythmogenic cardiomyopathy and left ventricular non-compaction (LVNC).
The Laboratory for Molecular Medicine at Personalized Medicine offers the following cardiomyopathy tests.
PanCardiomyopathy Panel (62 Genes) Test
Inherited cardiomyopathies are a group of genetically heterogeneous cardiac diseases with a relatively high population frequency, association with sudden cardiac death, and substantial genetic component. Familial inheritance is common and typically follows an autosomal dominant pattern, though all other forms of inheritance exist. The predominant forms are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), followed by arrhythmogenic cardiomyopathy and left ventricular non-compaction (LVNC).
This test is used for:
- Cases with an unclear diagnosis
- Diagnoses where the genetic contribution is incompletely characterized (e.g., LVNC, RCM)
- Comprehensive testing
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, LLC (27 Blue Sky Drive, Burlington, MA 01803; 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.
Requisition form
All samples must be accompanied with a completed requisition form. Please make sure any identifiers used on the specimen are provided on the paperwork. Consent page should be signed by a health care provider. Any incomplete or missing paperwork may delay the start of testing.
Ordering
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Test code: lmPCM-pnlAv6_L
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Turnaround time: 6-8 weeks
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Specimen required:
- 7ml of whole blood (3-5ml for an infant) in a lavender top tube (K2EDTA or K3EDTA) OR
- 10 ug of DNA at a minimum concentration of 25 ng/ul (please provide DNA concentration)
If providing DNA, please provide name and CLIA # of lab performing blood extraction.
Billing information
The Laboratory for Molecular Medicine offers several billing options for our clients and their patients; however, we do not bill insurance companies and are unable to begin testing without accurate billing information.
- CPT code: 81439
- Price: $1,200
Cardiomyopathy requisition form
Transthyretin Amyloidosis—TTR Gene Sequencing
TTR gene sequencing should be ordered for individuals with a clear or suspected diagnosis of TTR amyloidosis.
The most common presentation of transthyretin amyloidosis is neuropathic, which typically manifests as autonomic or sensory motor impairment. Cardiac involvement is frequent in transthyretin amyloidosis is frequent and most often takes the form of restrictive cardiomyopathy. The enlarged appearance of the interventricular septum and left ventricular muscle reflects the deposition of TTR in these structures rather than true hypertrophy. The symmetrical pattern of enlargement and histological appearance help differentiate this condition from other forms of hypertrophic cardiomyopathy. Additional cardiac symptoms can include arrhythmias, congestive heart failure and sudden death. Variants in TTR are a primary cause of transthyretin amyloidosis and the disease has a high prevalence in certain ethnic groups, such as African Americans.
Gene: TTR
Protein: Transthyretin
OMIN#: 176300
Locus: 18q12.1
This test is greater than 99.9% accurate in detecting variants in the sequence analyzed.
Sequencing of TTR detected more than 99% of disease-causing variant for transthyretin amyloidosis (GeneReviews). Learn more about transthyretin amyloidosis.
Requisition form
All samples must be accompanied with a completed requisition form. Please make sure any identifiers used on the specimen are provided on the paperwork. Consent page should be signed by a health care provider. Any incomplete or missing paperwork may delay the start of testing.
Ordering
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Test code: lmTTR-av2_
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Turnaround time: 3 weeksSpecimen required:
- 4-8ml of whole blood (3-5ml for an infant) in a lavender top tube (K2EDTA or K3EDTA) or
- 10 ug of DNA at a minimum concentration of 25 ng/ul (please provide DNA concentration)
If providing DNA, please provide name and CLIA # of lab performing blood extraction.
Billing information
The Laboratory for Molecular Medicine offers several billing options for our clients and their patients; however, we do not bill insurance companies and are unable to begin testing without accurate billing information.
- CPT code: 81404
- Price: $600