Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000456591 | SCV000543467 | uncertain significance | Long QT syndrome | 2020-10-30 | criteria provided, single submitter | clinical testing | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individuals affected with long QT syndrome (PMID: 19862833, 23158531, Invitae). ClinVar contains an entry for this variant (Variation ID: 67241). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 567 of the KCNH2 protein (p.Ile567Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
Ambry Genetics | RCV004017366 | SCV004849029 | uncertain significance | Cardiovascular phenotype | 2019-01-14 | criteria provided, single submitter | clinical testing | The c.1700T>C (p.I567T) alteration is located in exon 7 (coding exon 7) of the KCNH2 gene. This alteration results from a T to C substitution at nucleotide position 1700, causing the isoleucine (I) at amino acid position 567 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Cardiovascular Biomedical Research Unit, |
RCV000057952 | SCV000089472 | 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:19862833). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. |