Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000692137 | SCV000819946 | uncertain significance | Long QT syndrome | 2018-03-18 | criteria provided, single submitter | clinical testing | While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with valine at codon 260 of the KCNH2 protein (p.Ala260Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant has not been reported in the literature in individuals with KCNH2-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Ambry Genetics | RCV002406565 | SCV002673037 | uncertain significance | Cardiovascular phenotype | 2021-02-02 | criteria provided, single submitter | clinical testing | The p.A260V variant (also known as c.779C>T), located in coding exon 4 of the KCNH2 gene, results from a C to T substitution at nucleotide position 779. The alanine at codon 260 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available 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. |