Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825532 | SCV000966847 | likely pathogenic | Congenital long QT syndrome | 2018-03-23 | criteria provided, single submitter | clinical testing | The c.1591-1G>A variant in KCNQ1 has not been previously reported in individuals with long QT syndrome or in large population studies. This variant occurs in th e invariant region (+/- 1,2) of the splice consensus sequence and is predicted t o cause altered splicing leading to an abnormal or absent protein. Loss-of-funct ion variants in KCNQ1 are associated with LQTS (also known as Romano-Ward syndro me) in the heterozygous state and with Jervell and Lange-Nielsen syndrome (JLNS) in the compound heterozygous or homozygous state. In summary, although addition al studies are required to fully establish its clinical significance, the c.1591 -1G>A variant is likely pathogenic. ACMG Criteria applied (Richards 2015): PM2; PVS1_Strong. |
| Invitae | RCV001388701 | SCV001589776 | pathogenic | Long QT syndrome | 2020-08-01 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 30369311). This variant has been observed in individual(s) with long QT syndrome (PMID: 30369311, 26675252). ClinVar contains an entry for this variant (Variation ID: 666975). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 12 of the KCNQ1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as Pathogenic. |