Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621150 | SCV000735422 | uncertain significance | Cardiovascular phenotype | 2016-06-17 | criteria provided, single submitter | clinical testing | The p.P400A variant (also known as c.1198C>G), located in coding exon 9 of the KCNQ1 gene, results from a C to G substitution at nucleotide position 1198. The proline at codon 400 is replaced by alanine, an amino acid with highly similar properties. 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 6501 samples (13002 alleles) with coverage at this position. This amino acid position is poorly conserved in available vertebrate species, and alanine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000818634 | SCV000959258 | uncertain significance | Long QT syndrome | 2023-06-23 | criteria provided, single submitter | clinical testing | 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt KCNQ1 protein function. ClinVar contains an entry for this variant (Variation ID: 518535). This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 400 of the KCNQ1 protein (p.Pro400Ala). |
| Color Diagnostics, |
RCV001841785 | SCV001354372 | likely benign | Cardiac arrhythmia | 2018-11-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002281118 | SCV002569832 | uncertain significance | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function |
| All of Us Research Program, |
RCV000818634 | SCV004836402 | likely benign | Long QT syndrome | 2023-08-08 | criteria provided, single submitter | clinical testing |