Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000182161 | SCV000234464 | likely pathogenic | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16244680, 19716085, 18752142, 19862833, 34319147, 34505893, 26132555) |
| Labcorp Genetics |
RCV000190169 | SCV001576508 | pathogenic | Long QT syndrome | 2024-03-29 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 7 of the KCNQ1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with long QT syndrome (PMID: 16244680, 19716085, 26132555, 34319147, 34505893). ClinVar contains an entry for this variant (Variation ID: 52937). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV003162395 | SCV003900177 | pathogenic | Cardiovascular phenotype | 2022-12-29 | criteria provided, single submitter | clinical testing | The c.1032+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 7 of the KCNQ1 gene. This alteration has been reported in subjects with features of long QT syndrome (LQTS) and was shown to segregate with disease in one family (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303; Shigemizu D et al. PLoS One, 2015 Jul;10:e0130329; Choi SH et al. Circ Genom Precis Med, 2021 Aug;14:e003300). Another alteration impacting the same site (c.1032G>A (p.A344A)) has been shown to have a similar impact on splicing (Wuriyanghai Y et al. Heart Rhythm, 2018 Oct;15:1566-1574). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Medical Research Institute, |
RCV000190169 | SCV000222019 | likely pathogenic | Long QT syndrome | no assertion criteria provided | research |