Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002428783 | SCV002743854 | uncertain significance | Cardiovascular phenotype | 2022-10-25 | criteria provided, single submitter | clinical testing | The p.S890C variant (also known as c.2669C>G), located in coding exon 11 of the KCNH2 gene, results from a C to G substitution at nucleotide position 2669. The serine at codon 890 is replaced by cysteine, an amino acid with dissimilar properties. This alteration has been reported in a long Q syndrome (LQTS) cohort (Riuró H et al. Eur J Hum Genet, 2015 Jan;23:79-85). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003102092 | SCV003440231 | uncertain significance | Long QT syndrome | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 890 of the KCNH2 protein (p.Ser890Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with KCNH2-related conditions (PMID: 24667783). 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 tolerated. 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. |