Pan Cardiomyopathy Panel (62 Genes) - Clinical Genetic Test - GTR

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Pan Cardiomyopathy Panel (62 Genes)

Clinical Genetic Test

offered by

Laboratory for Molecular Medicine

View lab's test page

GTR Test Accession: GTR000509149.12

INHERITED DISEASEMUSCULOSKELETALCARDIOVASCULAR ... View more

Last updated in GTR: 2023-12-04

Last annual review date for the lab: 2023-12-01

At a Glance

Test purpose:

Diagnosis

Conditions (100):

Primary dilated cardiomyopathy; 3-Methylglutaconic aciduria type 2; Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; ...

Genes (61):

ABCC9 (12p12.1), ACTC1 (15q14), ACTN2 (1q43), ANKRD1 (10q23.31), BAG3 (10q26.11), ...

Methods (2):

Molecular Genetics - Deletion/duplication analysis: VisCap analysis; ...

Target population:

Individuals with cardiomyopathy, specifically HCM, DCM, ARVC, LVNC, or RCM.

Clinical validity:

The detection rate of the Pan Cardiomyopathy Panel is approximately …

Clinical utility:

Not provided

Ordering Information

Offered by:

Laboratory for Molecular Medicine
View lab's website
View lab's test page

Test short name:

PCM Panel

Specimen Source:

Isolated DNA
Peripheral (whole) blood
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant
Registered Nurse

Test Order Code:

lmPCM-pnlAv6_L
View other test codes

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Yes

Test strategy:

Inherited cardiomyopathies are a group of genetically heterogeneous cardiac diseases that are relatively common in the general population They are associated with heart failure and sudden cardiac death and have a substantial genetic component. Familial inheritance is common and typically follows an autosomal dominant pattern, though other inheritance are also … View more

View citations (1)

Teekakirikul P, Kelly MA, Rehm HL, Lakdawala NK, Funke BH. Inherited cardiomyopathies: molecular genetics and clinical genetic testing in the postgenomic era. J Mol Diagn. 2013;15(2):158-70. doi:10.1016/j.jmoldx.2012.09.002. Epub 2012 Dec 27. PMID: 23274168.

Pre-test genetic counseling required:

Post-test genetic counseling required:

Recommended fields not provided:

Lab contact for this test

Conditions

Total conditions: 100

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 61

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument

Deletion/duplication analysis

VisCap analysis

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Illumina NextSeq 550

Clinical Information

Test purpose:

Diagnosis

Clinical validity:

The detection rate of the Pan Cardiomyopathy Panel is approximately 35% for HCM, ~37% for DCM and ~50% for ARVC. The detection rate for the other cardiomyopathies remains unknown.

View citations (2)

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014;16(8):601-8. doi:10.1038/gim.2013.204. Epub 2014 Feb 06. PMID: 24503780.
Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015;17(11):880-8. doi:10.1038/gim.2014.205. Epub 2015 Jan 22. PMID: 25611685.

Target population:

Individuals with cardiomyopathy, specifically HCM, DCM, ARVC, LVNC, or RCM.

View citations (1)

Teekakirikul P, Kelly MA, Rehm HL, Lakdawala NK, Funke BH. Inherited cardiomyopathies: molecular genetics and clinical genetic testing in the postgenomic era. J Mol Diagn. 2013;15(2):158-70. doi:10.1016/j.jmoldx.2012.09.002. Epub 2012 Dec 27. PMID: 23274168.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
All VUS's are reported

Are family members with defined clinical status recruited to assess significance of VUS without charge?
Yes. *Please call. Offered on a case-by-case basis.

Will the lab re-contact the ordering physician if variant interpretation changes?
No. Ordering provider is encouraged to periodically contact the lab to see if there is any new information available. However, if the ordering physician has GeneInsight Clinic, they may receive automatic updates on classification through that program.

Research:

Is research allowed on the sample after clinical testing is complete?
No

Recommended fields not provided:

Clinical utility, Sample negative report, Sample positive report

Technical Information

Test Procedure:

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* … 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. View more

Test Platform:

Agilent SureSelect

Test Confirmation:

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

Test Comments:

The Pan Cardiomyopathy Panel (62 genes) offers comprehensive screening for HCM, DCM, RCM, LVNC, ARVC, and CPVT.

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

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%).

Assay limitations:

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 i nformation, such … View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Intra-Laboratory

VUS:

Software used to interpret novel variations
Alamut, UCSC Genome Browser, gnomAD, ESP, 1000 Genomes, PolyPhen, SIFT, AlignGVGD, and more.

Laboratory's policy on reporting novel variations
All novel VUS's are reported

Recommended fields not provided:

Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, PT Provider, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View ACTC1 variations in ClinVar

View ACTN2 variations in ClinVar

View DES variations in ClinVar

View DSG2 variations in ClinVar

View EYA4 variations in ClinVar

View FKTN variations in ClinVar

View LMNA variations in ClinVar

View MYBPC3 variations in ClinVar

View MYH6 variations in ClinVar

View PLN variations in ClinVar

View PSEN1 variations in ClinVar

View PSEN2 variations in ClinVar

View SGCD variations in ClinVar

View TAFAZZIN variations in ClinVar

View TMPO variations in ClinVar

View TNNT2 variations in ClinVar

View TPM1 variations in ClinVar

View TTN variations in ClinVar

View VCL variations in ClinVar

View CSRP3 variations in ClinVar

View TCAP variations in ClinVar

View BAG3 variations in ClinVar

View ABCC9 variations in ClinVar

View LDB3 variations in ClinVar

View ANKRD1 variations in ClinVar

View NEXN variations in ClinVar

View RBM20 variations in ClinVar

RefSeqGene

Consumer resources:

MedlinePlusGenetics (GHR)

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.