PMC Hypertrophic Cardiomyopathy (HCM) Panel

Associated Conditions
- Acyl-CoA dehydrogenase family, deficiency
- Acyl-CoA dehydrogenase, very long chain, deficiency
- Amyloidosis, hereditary, transthyretin-related
- Amyloidosis, systemic nonneuronopathic
- Atrial fibrillation
- Atrial septal defect
- Brugada syndrome
- Cantu syndrome
- Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency
- Cardiofaciocutaneous syndrome
- Cardiomyopathy, familial hypertrophic
- Cardiomyopathy, restrictive
- Carnitine palmitoyltransferase II deficiency
- Combined oxidative phosphorylation deficiency 17
- Combined oxidative phosphorylation deficiency 31
- Congenital myopathy with excess of muscle spindles
- Costello syndrome
- Danon disease
- Dilated cardiomyopathy (DCM)
- Dystransthyretinemic hyperthyroxinemia
- Emery-Dreifuss muscular dystrophy
- Epidermolysis bullosa simplex, generalized, with scarring and hair loss
- Fabry disease
- Friedreich ataxia
- Glycogen storage disease
- Glycogen storage disease of heart, lethal congenital
- Hypertrophic cardiomyopathy (HCM)
- Hypoalphalipoproteinemia
- Infantile type I muscle fibre disease and cardiomyopathy
- Left ventricular noncompaction
- Leigh syndrome
- LEOPARD syndrome
- Metachondromatosis
- Mitochondrial complex I deficiency
- Mitochondrial DNA depletion syndrome
- Myopathy
- Myopathy with postural muscle atrophy
- Myopathy, Cardiomyopathy
- Myopathy, distal
- Myopathy, myofibrillar
- Myopathy, myosin storage
- Neurodevelopmental disorder
- Noonan syndrome
- Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
- Pediatric cardiomyopathy
- Progressive external ophthalmoplegia with mitochondrial DNA deletions
- Reducing bod myopathy
- Scapuloperoneal syndrome, neurogenic, Kaeser type
- Sengers syndrome, Cataract 38
- Timothy syndrome
- Vici syndrome
- Wolff-Parkinson-White syndrome

Methodology

Targeted Exome/ Slice Exome (Next Generation Sequencing including Copy Number Variation)

Coverage

120x

Assay Information
- ACTC1: Sequencing analysis for exons 6 includes only cds +/- 10 bp.
- ACTN2: Deletion/duplication analysis is not offered for exon 9.
- ANKRD1: Deletion/duplication analysis is not offered for exons 3-4. Sequencing analysis for exons 4 includes only cds +/- 10 bp.
- CACNA1C: Deletion/duplication and sequencing analysis is not offered for exons 44-45.
- FLNC: Deletion/duplication analysis is not offered for exon 47. Sensitivity and specificity for single nucleotide variants| insertions and deletions in exons 47-48 may be reduced due to the presence of segmental duplications overlapping the region.
- GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
- GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
- MYBPC3: Analysis includes the intronic variants NM_000256.3:c.1224-52G>A and c.3628-41_3628-17del25.

Ordering information

Turnaround Time: 10 business days

Preferred Speciment: Saliva Kits (available upon request)

Alternate Specimens: Nail clippings or 3-mL whole blood in purple top EDTA tube

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Limitations

All sequencing technologies have limitations. A negative result from this analysis does not rule out a possible genetic diagnosis as some variants may not be detected by this test. This test is not designed to detect low level mosaicism, structural rearrangements, indels >40bp, deep intronic variants of unknown clinical significance, or large cytogenetic CNVs. Certain inherent qualities of the human genome, for example repetitive regions/homopolymers, GC rich, pseudogenes, and rare polymorphisms, pose significant technical challenges such as sequence misalignment that may potentially impact the accuracy of the results. False negative results may also occur in the setting of allogeneic bone marrow, stem cell transplantation, active or chronic hematologic conditions, recent blood transfusions, suboptimal DNA quality or PCR trace contamination. Other potential sources of error include sample mix-ups and clerical issues.

References
- 1. Richards S et al. Genetics in medicine. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 2015 May;17(5):405-24 (PMID: 25741868)
- 2. GnomAD (gnomAD)
- 3. CSPEC (ClinGen variant classification rules registry) Criteria Specification Registry
- 4. Normal copy number variation in healthy individuals database of genomic variants: http://dgv.tcag.ca/dgv/app/home
- 5. Riggs, E.R., Andersen, E.F., Cherry, A.M. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22, 245–257 (2020). https://doi.org/10.1038/s41436-019-0686-8
- 6. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437.
- 7. Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), Copyright® 1966-2012. World Wide Web URL: http://omim.org.
- 8. http://tinyurl.com/ACMGv4 (ACMG/ Clingen draft Interpretation SOP); clingen_variant-curation_sopv1.pdf

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Test Description

Associated Conditions

Methodology

Coverage

Assay Information

Ordering information

Limitations

References

Tagged Genes