Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular and Cytogenetics Laboratory, |
RCV001580151 | SCV001805856 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 3 | 2021-08-05 | criteria provided, single submitter | clinical testing | To date, the Arg248Cysfs*8 variant in TECRL has never been reported as a pathogenic variant in the medical literature. It was detected in 2 siblings (9-year-old boy and 13-year-old girl) with a mixed phenotype of Long QT syndrome and Catecholaminergic polymorphic ventricular tachycardia (CPVT), in the context of positive family history of sudden death in their 2 siblings at a young age (the sister who has been previously healthy collapsed at the age of 16 years while climbing stairs and she could not be resuscitated. The brother who did have mild developmental delay collapsed at the age of 5 years after shocking as he went immediately flaccid without initiating reflex). No molecular or tissue autopsy done for any of the deceased victims. The variant was detected in the homozygous state in the 2 probands and in heterozygosity in each of the consanguineous parents (both asymptomatic, normal cardiac workup), suggesting an autosomal recessive inheritance. This variant creates a shift in the reading frame starting at codon 248. The new reading frame ends in a stop codon 8 positions downstream. This variant is absent in general population databases (gnomAD, 1000 Genomes Project and ExAC). Pathogenic variants in the TECRL gene are known to be associated with autosomal recessive CPVT type 3, characterized by overlapping characteristics of Long QT and CPVT (Devalla 2016, Bhuiyan 2007, Xie 2019). In summary, the Arg248Cysfs*8 variant meets the criteria to be classified as “Likely pathogenic†according to ACMG guidelines. |