Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000182292 | SCV000234595 | pathogenic | not provided | 2024-12-17 | criteria provided, single submitter | clinical testing | Reported in patients with LQTS referred for genetic testing at GeneDx and in published literature (PMID: 19716085, 34505893); Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31447099, 34505893, 19716085) |
| Laboratory for Molecular Medicine, |
RCV000609648 | SCV000713069 | likely pathogenic | Congenital long QT syndrome; Jervell and Lange-Nielsen syndrome | 2017-05-18 | criteria provided, single submitter | clinical testing | The p.Val135fs variant in KCNQ1 has been reported in 1 individual that was refer red for long QT syndrome (LQTS) testing (Kapplinger 2009) and has also been repo rted in ClinVar (Variation ID# 200891). This variant was absent from large popul ation studies, though the ability of these studies to accurately detect indels m ay be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 135 and leads to a prematur e termination codon 102 amino acids downstream. This alteration is then predicte d to lead to a truncated or absent protein. Loss-of-function variants in KCNQ1 are associated with LQTS (also known as Romano-Ward syndrome) in the heterozygou s state and with Jervell and Lange-Nielsen syndrome (JLNS) in the compound heter ozygous or homozygous state. In summary, although additional studies are require d to fully establish its clinical significance, the p.Val135fs variant is likely pathogenic. |
| Labcorp Genetics |
RCV003532029 | SCV004294059 | pathogenic | Long QT syndrome | 2023-01-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val135Serfs*102) 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 (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features consistent with long QT syndrome (PMID: 19716085, 34505893). ClinVar contains an entry for this variant (Variation ID: 200891). For these reasons, this variant has been classified as Pathogenic. |