Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000531823 | SCV000648492 | uncertain significance | Brugada syndrome 6 | 2025-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 32 of the KCNE3 protein (p.Arg32Gln). This variant is present in population databases (rs745645715, gnomAD 0.005%). This missense change has been observed in individual(s) with sudden infant death syndrome (PMID: 37589201). ClinVar contains an entry for this variant (Variation ID: 470686). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| ARUP Laboratories, |
RCV000531823 | SCV001159900 | uncertain significance | Brugada syndrome 6 | 2018-09-18 | criteria provided, single submitter | clinical testing | The KCNE3 c.95G>A; p.Arg32Gln variant (rs745645715), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 470686). This variant is found on seven chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 32 is moderately conserved, but it occurs as a glutamine in several vertebrate species, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Computational analyses of splicing (Alamut v.2.11) predict that this variant may create a novel cryptic acceptor splice site, but mRNA studies would be required to confirm if splicing occurs at this site. Given the lack of clinical and functional data, the significance of the p.Arg32Gln variant is uncertain at this time. |
| Ambry Genetics | RCV002384193 | SCV002694803 | uncertain significance | Cardiovascular phenotype | 2024-07-20 | criteria provided, single submitter | clinical testing | The p.R32Q variant (also known as c.95G>A), located in coding exon 1 of the KCNE3 gene, results from a G to A substitution at nucleotide position 95. The arginine at codon 32 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
| Fulgent Genetics, |
RCV000531823 | SCV002780833 | uncertain significance | Brugada syndrome 6 | 2021-10-30 | criteria provided, single submitter | clinical testing |