Genetic testing for cardiac arrhythmia of unknown type (Molecular Autopsy) (R138)

Background information

Detailed interpreted clinical information is valuable to aiding variant interpretation.

The testing repertoire also includes a number of different arrhythmogenic and cardiomyopathy disorders which may include additional features as part of the clinical presentation.

There are 53 genes and one variant included on this panel. The genes are: ACTC1, ACTN2, BAG3, CACNA1C, CALM1, CALM2, CALM3, CASQ2, CDH2, CSRP3, DES, DMD, DOLK, DSC2, DSG2, DSP, EMD, FHL1, FHOD3, FLNC, GLA, HCN4, JPH2, JUP, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, LAMP2, LMNA, MYBPC3, MYH7, MYL2, MYL3, NEXN, NKX2-5, PKP2, PLN, PRKAG2, RBM20, RYR2, SCN5A, TMEM43, TNNC1, TNNI3, TNNI3K, TNNT2, TPM1, TRDN, TTN, TTR, and VCL.

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. The mitochondrial variant MT-TI m.4300A>G is the single mitochondrial variant included on the panel. Variants of uncertain significance in PKP2 and DSP are not reported (only when detected in the R138 panel).

Testing strategy

Clinically affected probands:

R138 - Singleton analysis of a large panel of genes. Data from the entire coding region of the main transcripts of KCNQ1, KCNH2, and SCN5A is always included. In addition, data from the key coding regions (codons 44 to 466, 2147-2534 and 3778-4959) of the main transcript of RYR2 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)