Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000455396 | SCV000539445 | uncertain significance | not specified | 2016-07-26 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 LQT proband (PMID 19716085), functional study (PMID 25417810) shows this variant does not impact trafficking |
| Invitae | RCV000684931 | SCV000812394 | uncertain significance | Long QT syndrome | 2023-02-10 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1078 of the KCNH2 protein (p.Tyr1078Cys). This variant is present in population databases (rs199473029, gnomAD 0.002%). This missense change has been observed in individual(s) with KCNH2-related conditions (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67483). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change does not substantially affect KCNH2 function (PMID: 19841300, 25348405, 25417810). 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. |
| Fulgent Genetics, |
RCV002504965 | SCV002815412 | uncertain significance | Short QT syndrome type 1; Long QT syndrome 2 | 2021-11-12 | criteria provided, single submitter | clinical testing | |
| Cardiovascular Biomedical Research Unit, |
RCV000058212 | SCV000089732 | 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. |