Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004521065 | SCV005037081 | uncertain significance | Cardiovascular phenotype | 2023-12-06 | criteria provided, single submitter | clinical testing | The p.K4650E variant (also known as c.13948A>G), located in coding exon 96 of the RYR2 gene, results from an A to G substitution at nucleotide position 13948. The lysine at codon 4650 is replaced by glutamic acid, an amino acid with similar properties. This variant has been detected in an adolescent with aborted sudden cardiac death who was subsequently, reportedly, diagnosed with catecholaminergic polymorphic ventricular tachycardia (Hofman N et al. Pediatrics, 2007 Oct;120:e967-73; Kapplinger JD et al. Circ Genom Precis Med. 2018 Feb;11(2):e001424). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |