Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001901530 | SCV002172337 | uncertain significance | Long QT syndrome | 2022-08-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1404204). 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. This missense change has been observed in individual(s) with premature unexpected and unexplained sudden cardiac death (PMID: 31337358). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 855 of the KCNH2 protein (p.Ser855Asn). This variant is not present in population databases (gnomAD no frequency). |
Ambry Genetics | RCV002425215 | SCV002740245 | uncertain significance | Cardiovascular phenotype | 2021-03-17 | criteria provided, single submitter | clinical testing | The p.S855N variant (also known as c.2564G>A), located in coding exon 10 of the KCNH2 gene, results from a G to A substitution at nucleotide position 2564. The serine at codon 855 is replaced by asparagine, an amino acid with highly similar properties, and is located in the C-terminal region of the protein. This variant was detected in a sudden arrhythmic death syndrome cohort; however, clinical details were limited (Raju H et al. BMC Cardiovasc Disord, 2019 07;19:174). This amino acid position is not well conserved in available vertebrate species, and asparagine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |