Genetic testing for dilated and arrhythmogenic cardiomyopathy (DCM) (R132)

Background information

Often individuals present with reduced exercise tolerance or dyspnoea. More severe signs of heart failure may ensue in some cases if left untreated. Some affected individuals also have cardiac conduction defects. The later stages of hypertrophic cardiomyopathy (HCM) can also resemble DCM; this is known as 'burnt out' HCM.

DCM is highly genetically heterogeneous, with numerous implicated genes. A significant portion (up to 20 percent) of pathogenic or likely pathogenic variants are identified in TTN. DSP, LMNA, MYBPC3, MYH7, PKP2, RBM20, SCN5A, TNNT2, and TPM1 all each account for a few percent of cases and the other genes cause DCM more rarely.

Due to a lack of data to aid interpretation missense variants in TTN are not reported and only potentially truncating TTN variants are reported. The missense data is retained in the laboratory and may be analysed in the future.

There are currently 31 genes (ACTC1, ACTN2, BAG3, CDH2, DES, DMD, DOLK, DSC2, DSG2, DSP, EMD, FLNC, JUP, LAMP2, LMNA, MYBPC3, MYH7, NEXN, NKX2-5, PKP2, PLN, RBM20, SCN5A, TMEM43, TNNC1, TNNI3, TNNI3K, TNNT2, TPM1, TTN, and VCL) together with one deletion variant (deletion of exon three RYR2) included on the panel.

Testing strategy

Clinically affected probands:

R132 - Singleton analysis of a large panel of genes. Data from the entire coding region of the main transcripts of DSP, LMNA, MYH7, TNNT2, and TPM1 is always included.

Targeted analysis for known / previously reported familial variants:

• Family testing in clinically unaffected family members at risk of inheriting a previously reported familial pathogenic variant (R242)
• Diagnostic confirmation in individuals at risk of inheriting a previously reported familial pathogenic variant and clinically suspected of having the familial condition (R240)
  
• Segregation studies in affected family members to aid variant interpretation (R375)
  
• Prenatal diagnosis for families with a pathogenic or likely pathogenic variant identified (R240 and R321 Maternal cell contamination)

Target reporting times

• 84 calendar days for diagnostic screening of affected individuals
  
• 42 calendar days for diagnostic confirmation in individuals at risk of inheriting a previously reported familial pathogenic variant and clinically suspected of having the familial condition (R240)
  
• 14 calendar days for presymptomatic testing of clinically unaffected family members at risk of inheriting a previously reported familial pathogenic variant (R242)

Turnaround times for genetic / genomic testing

Sample requirements and referring samples

All non NHSE referrals should be accompanied by a completed referral form.

Requesting specialties:

• Cardiology
• Clinical Genetics
• Paediatrics
• Electrophysiology
• Pathology
• Coroners

Specimen requirements and referring samples

Price list for non NHSE referrals (pdf)