Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001941481 | SCV002217928 | uncertain significance | Brugada syndrome | 2020-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 96 of the KCNE5 protein (p.Gln96Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KCNE5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004043182 | SCV002745912 | uncertain significance | not specified | 2022-07-17 | criteria provided, single submitter | clinical testing | The p.Q96E variant (also known as c.286C>G), located in coding exon 1 of the KCNE5 gene, results from a C to G substitution at nucleotide position 286. The glutamine at codon 96 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |