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GeneSeq®: Cardio Familial Cardiomyopathy Profile
This test covers all coding nucleotides of 46 genes: ABCC9, ACTC1, ACTN2, ALMS1, APOA1, CAV3, CSRP3, CTF1, DES, DNAJC19, DSC2, DSG2, DSP, DTNA, EMD, EYA4, FKTN, GLA, HOPX, JUP, LAMP2, LDB3, LMNA, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, PLN, PKP2, PRKAG2, RYR2, SCN5A, SGCD, TAZ, TCAP, TGFB3, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTR, and VCL; plus at least two and typically 10 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 10 flanking nucleotides in the 5′ and 3′ UTR.
Confirm a clinical diagnosis of Cardiomyopathy and identify presymptomatic family member, guiding prophylactic measures.
This analysis does not rule out germline mosaicism, the presence of large chromosomal aberrations (including deletions, insertions, and rearrangements), mutations in regions or genes not included in this test, and possible inter/intragenic interactions between sequence variants. False-positive or false-negative results may occur for reasons that include genetic variants, blood transfusions, bone marrow transplantation, mislabeled specimens, or erroneous representation of family relationships.
Mutation analysis is performed using the Agilent Sure Select XT® enrichment method and the Illumina® next-generation sequencing platform. Regions of the interest include all exons and splice junctions for each gene and limited regions for the following: SHOC2 (exon 2), APOB (556bp of exon 26), and AKAP9 (exon 18). Sequencing reads are aligned with the hg19 build of the human genome reference sequence. Analytical sensitivity is based on the depth of coverage across the regions of the interest and is provided separately for each gene. Greater than 98% of target bases are synonymous variants not previously recorded at ≥20x coverage. Sanger sequencing is used to confirm mutation identity and analyze regions with low coverage. Variants are reported using numbering and nomenclature recommended by the Human Genome Variation Society (HGVS). Variants known to be benign and synonymous variants not previously recorded in our internal variant data bases are not reported.
Cardiomyopathies are generally characterized by weakening and impaired contractile function of the myocardium that leads to ventricular hypertrophy or dilation. Myocardial dysfunction associated with cardiomyopathy can either be of mechanical or electrical etiology. The four major types of cardiomyopathy include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), and restrictive cardiomyopathy (RCM). Rarer types include left ventricular noncompaction (LVNC) and the amyloid-associated cardiomyopathies, such as transthyretin (TTR) amyloidosis and apolipoprotein A-1 amyloidosis (AApoA-1).
Many cardiomyopathies are now recognized as familial conditions that may be transmitted in an autosomal dominant, autosomal recessive, X-linked, or mitochondrial manner. Genetic testing for the presence of germline mutations in the genes known to be associated with cardiomyopathy may:
• Confirm a diagnosis of familial cardiomyopathy.
• Identify which subtype of a particular cardiomyopathy.
• Identify family members of an index patient who harbor the familial mutation and may wish to undergo cardiac screening at regular intervals.
• Facilitate appropriate genetic counseling for family members.
10 mL whole blood or 30 mL if ordering multiple tests
Yellow-top (ACD) tube or lavender-top (EDTA) tube
Maintain specimen at room temperature.
Causes for Rejection
Frozen specimen; container broken or leaking; container not labeled or label not legible; improper anticoagulant
Test orders must include an attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form: Consent for Genetic Testing. Please call customer service at 866-647-0735 before submitting specimens for family testing (ie, known mutations).