Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003647742 | SCV004467280 | uncertain significance | Long QT syndrome | 2023-04-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of long QT syndrome (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67373). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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 sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 728 of the KCNH2 protein (p.Ile728Phe). |
| All of Us Research Program, |
RCV003647742 | SCV004835337 | uncertain significance | Long QT syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004017369 | SCV004849033 | uncertain significance | Cardiovascular phenotype | 2017-12-28 | criteria provided, single submitter | clinical testing | The c.2182A>T (p.I728F) alteration is located in exon 9 (coding exon 9) of the KCNH2 gene. This alteration results from a A to T substitution at nucleotide position 2182, causing the isoleucine (I) at amino acid position 728 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV004719690 | SCV005325353 | uncertain significance | not provided | 2024-01-26 | criteria provided, single submitter | clinical testing | Reported in two patients with long QT syndrome in published literature (PMID: 19716085); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19716085) |
| Cardiovascular Biomedical Research Unit, |
RCV000058093 | SCV000089613 | 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. |