Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003531965 | SCV004297379 | uncertain significance | Long QT syndrome | 2022-11-12 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Lys70 amino acid residue in KCNE1. Other variant(s) that disrupt this residue have been observed in individuals with KCNE1-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects KCNE1 function (PMID: 21576493). ClinVar contains an entry for this variant (Variation ID: 132663). This missense change has been observed in individuals with clinical features of long QT syndrome (PMID: 31941373; Invitae). This variant is present in population databases (rs199473646, gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 70 of the KCNE1 protein (p.Lys70Met). |
| Cardiovascular Biomedical Research Unit, |
RCV000119075 | SCV000153794 | not provided | Congenital long QT syndrome | no assertion provided | literature only | This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. |