Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001841142 | SCV001359266 | uncertain significance | Cardiac arrhythmia | 2023-06-21 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with lysine at codon 220 of the KCNQ1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with sudden unexplained death (PMID: 26228265). This variant has also been identified in 10/249844 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
All of Us Research Program, |
RCV004010507 | SCV004838771 | uncertain significance | Long QT syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with lysine at codon 220 of the KCNQ1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with sudden unexplained death (PMID: 26228265). This variant has also been identified in 10/249844 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV004033425 | SCV005033424 | uncertain significance | Cardiovascular phenotype | 2024-02-13 | criteria provided, single submitter | clinical testing | The p.Q220K variant (also known as c.658C>A), located in coding exon 4 of the KCNQ1 gene, results from a C to A substitution at nucleotide position 658. The glutamine at codon 220 is replaced by lysine, an amino acid with similar properties. This variant has been detected in an individual from a sudden unexplained death cohort (Stattin EL et al. Int J Legal Med, 2016 Jan;130:59-66). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |