Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: CA1801

The Blueprint Genetics Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Panel is a 29-gene test for genetic diagnostics of patients with clinical suspicion of left ventricular non-compaction cardiomyopathy (LVNC).

In majority of the cases familial cardiomyopathies, such as left ventricular non-compaction cardiomyopathy (LVNC), are inherited in an autosomal dominant manner. In rare instances, these conditions are inherited in an autosomal recessive pattern. In other rare cases, the cardiomyopathy can be inherited in an X-linked pattern. Establishing genetic diagnosis confirms or modifies the clinical diagnosis and enables disease specific estimates on prognostics and treatment paths. Genetic diagnosis enables effective family member risk stratification and preventive measures for the mutation carriers. The LVNC Panel is included in the Cardiomyopathy Panel and the Comprehensive Cardiology Panel.

About Left Ventricular Non-Compaction Cardiomyopathy (LVNC)

Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by a spongy appearance of the left ventricle and prominent trabeculations. Individuals may be asymptomatic, but common symptoms include arrhythmias, heart failure, and thromboembolism. LVNC can be seen in the context of congenital structural heart disease in children. LVNC is considered to have a significant amount of overlap with hypertrophic (HCM) and dilated cardiomyopathies (DCM). Many patients with clinical diagnosis of LVNC carry established mutations normally found in patients with clinical diagnosis of HCM or DCM. As the understanding of LVNC phenotype is still poorly understood we recommend testing of sarcomere genes associated with HCM and genes associated with DCM phenotype in cases with LVNC.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal

Genes in the Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ABCC9 Atrial fibrillation, Cantu syndrome, Dilated cardiomyopathy (DCM) AD 18 31
BAG3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 21 48
DES Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD/AR 51 95
DMD Becker muscular dystrophy, Duchenne muscular dystrophy, Dilated cardiomyopathy (DCM) XL 489 3390
DSC2 Arrhythmogenic right ventricular dysplasia with palmoplantar keratoderma and woolly hair, Arrhythmogenic right ventricular dysplasia AD/AR 16 66
DSG2 Arrhythmogenic right ventricular dysplasia, Dilated cardiomyopathy (DCM) AD 32 102
DSP Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis, Arrhythmogenic right ventricular dysplasia, familial, Cardiomyopathy, dilated, with wooly hair and keratoderma AD/AR 101 195
EMD Emery-Dreifuss muscular dystrophy XL 28 111
FBXO32 Dilated cardiomyopathy (DCM) AD/AR 2
HCN4 Sick sinus syndrome, Brugada syndrome AD 7 24
JPH2 Hypertrophic cardiomyopathy (HCM) AD 4 10
JUP Arrhythmogenic right ventricular dysplasia, Naxos disease AD/AR 10 28
LAMP2 Danon disease XL 46 81
LMNA Heart-hand syndrome, Slovenian, Limb-girdle muscular dystrophy, Muscular dystrophy, congenital, LMNA-related, Lipodystrophy (Dunnigan), Emery-Dreiffus muscular dystrophy, Malouf syndrome, Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford type AD/AR 183 458
MYBPC3 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 390 707
MYH6 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 9 61
MYH7 Hypertrophic cardiomyopathy (HCM), Myopathy, myosin storage, Myopathy, distal, Dilated cardiomyopathy (DCM) AD 285 748
PKP2* Arrhythmogenic right ventricular dysplasia AD 94 229
PLEKHM2 Dilated cardiomyopathy (DCM), left ventricular noncompaction AD/AR 1 1
PLN Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD/AR 8 21
RAF1 LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM) AD 37 42
RBM20 Dilated cardiomyopathy (DCM) AD 13 22
RYR2 Ventricular tachycardia, catecholaminergic polymorphic, Arrhythmogenic right ventricular dysplasia AD 114 287
SCN5A Heart block, nonprogressive, Heart block, progressive, Long QT syndrome, Ventricular fibrillation, Atrial fibrillation, Sick sinus syndrome, Brugada syndrome, Dilated cardiomyopathy (DCM) AD/AR/Digenic 193 795
TCAP Muscular dystrophy, limb-girdle, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD/AR 10 24
TNNT2 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM) AD 56 114
TPM1 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 36 62
TTN* Dilated cardiomyopathy (DCM), Tibial muscular dystrophy, Limb-girdle muscular dystrophy AD 437 226
VCL Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 12 19

*Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Gene Genomic location HG19 HGVS RefSeq RS-number Comment Reference
DMD ChrX:33192452 c.31+36947G>A NM_004006.2
DMD ChrX:31983146 c.6614+3310G>T NM_004006.2 rs797045526
DMD ChrX:31627738 c.8217+18052A>G NM_004006.2
DMD ChrX:31279780 c.9225-647A>G NM_004006.2 rs398124091
DMD ChrX:31279781 c.9225-648A>G NM_004006.2 rs398124084
DMD ChrX:32669100 c.961-5831C>T NM_004006.2 rs398124099
LMNA Chr1:156100609 c.513+45T>G NM_170707.3
MYBPC3 Chr11:47364832 c.1224-19G>A NM_000256.3 rs587776699
MYBPC3 Chr11:47359371 c.2309-26A>G NM_000256.3

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist

 

This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.

 

This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)

 

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a comprehensive Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Panel that covers classical genes associated with cardioegaly, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and left ventricular non-compaction cardiomyopathy (LVNC). The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ 81479
DEL/DUP 81479


ICD codes

Commonly used ICD-10 codes when ordering the Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Panel

ICD-10 Disease
I42.8 Left ventricular non-compaction cardiomyopathy (LVNC)

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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