Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018241 | SCV004848914 | likely pathogenic | Jervell and Lange-Nielsen syndrome | 2023-02-02 | criteria provided, single submitter | clinical testing | The c.1732+1G>T variant in KCNQ1 has not been previously reported in individuals with long QT syndrome or Jervell and Lange-Nielsen syndrome(JLNS) and was absent from large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Another splice site variant (c.1732+2T>C impacting the same exon has been reported in an individual with long QT. Loss of function of the KCNQ1 gene is an established disease mechanism in autosomal dominant long QT and autosomal recessive JLNS. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant long QT and autosomal recessive Jervell and Lange-Nielsen syndrome. ACMG/AMP criteria applied: PVS1_Strong, PM2_Supporting. |