Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482361 | SCV000565090 | uncertain significance | not provided | 2021-06-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26179811, 28600387, 30461122, 31941373, 26582918, 27535533) |
Invitae | RCV003532136 | SCV004297380 | uncertain significance | Long QT syndrome | 2023-05-11 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Long QT syndrome (PMID: 31941373). 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. This variant disrupts the p.Arg67 amino acid residue in KCNE1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31941373). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNE1 protein function. ClinVar contains an entry for this variant (Variation ID: 418269). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 67 of the KCNE1 protein (p.Arg67Leu). |
ARUP Laboratories, |
RCV000482361 | SCV004565137 | uncertain significance | not provided | 2023-05-10 | criteria provided, single submitter | clinical testing | The KCNE1 c.200G>T; p.Arg67Leu variant (rs79654911) is reported in the literature in individuals with idiopathic cardiac arrest or long QT syndrome (Mellor 2017, Roberts 2020). This variant is also reported in ClinVar (Variation ID: 418269). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.91). Due to limited information, the clinical significance of this variant is uncertain at this time. |