Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001953881 | SCV002246976 | pathogenic | Long QT syndrome | 2021-07-13 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with long QT syndrome (PMID: 26669661). This sequence change creates a premature translational stop signal (p.Val307Trpfs*47) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002370612 | SCV002687489 | pathogenic | Cardiovascular phenotype | 2019-02-12 | criteria provided, single submitter | clinical testing | The c.919delG pathogenic mutation, located in coding exon 6 of the KCNQ1 gene, results from a deletion of one nucleotide at nucleotide position 919, causing a translational frameshift with a predicted alternate stop codon (p.V307Wfs*47). This alteration has been reported in association with long QT syndrome (LQTS) (Haugaa KH et al. Heart Rhythm, 2013 Dec;10:1877-83; Seethala S et al. J Am Heart Assoc, 2015 Dec;4; Itoh H et al. Eur. J. Hum. Genet., 2016 08;24:1160-6). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Laboratory for Molecular Medicine, |
RCV004017886 | SCV004848019 | likely pathogenic | Congenital long QT syndrome | 2016-12-27 | criteria provided, single submitter | clinical testing | The p.Val307fs variant in KCNQ1 has not been previously reported in individuals with long QT syndrome and was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 307 and leads to a premature termination codon 47 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the KCNQ1 gene is an established disease mechanism in Long QT syndrome. In summary, although additional studies are required to fully establish its clinical significance, the p.Val307fs variant is likely pathogenic. |