Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000622052 | SCV000737483 | uncertain significance | Cardiovascular phenotype | 2016-03-31 | criteria provided, single submitter | clinical testing | The p.E4146G variant (also known as c.12437A>G), located in coding exon 90 of the RYR2 gene, results from an A to G substitution at nucleotide position 12437. The glutamic acid at codon 4146 is replaced by glycine, an amino acid with similar properties. An alteration affecting the same amino acid (p.E4146K) has been reported in association with sudden unexplained death (Tester DJ et al. Mayo Clin Proc. 2004;79(11):1380-4). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6052 samples (12104 alleles) with coverage at this position. 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 variant remains unclear. |