Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001841155 | SCV001359762 | uncertain significance | Cardiac arrhythmia | 2023-07-28 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 388 of the KCNQ1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with KCNQ1-related disorders in the literature. This variant has been identified in 2/251322 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. |
| Laboratory for Molecular Medicine, |
RCV001195498 | SCV001365876 | uncertain significance | not specified | 2020-04-02 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Asp388Asn variant in KCNQ1 has not been previously reported in individuals with Jervell and Lange Nielsen syndrome or Long QT syndrome, but was identified in 0.001% (2/113654) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Of note, two mammals have an asparagine (Asn) at this position, despite high nearby amino acid conservation. In summary, while the clinical significance of this variant is uncertain, conservation data suggest it is more likely to be benign. ACMG/AMP Criteria applied: PM2, BP4. |
| Ambry Genetics | RCV002320423 | SCV002632608 | uncertain significance | Cardiovascular phenotype | 2022-05-02 | criteria provided, single submitter | clinical testing | The p.D388N variant (also known as c.1162G>A), located in coding exon 9 of the KCNQ1 gene, results from a G to A substitution at nucleotide position 1162. The aspartic acid at codon 388 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available 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. |