Description
A variant of uncertain significance has been identified in the KCNQ1 gene. The K526E variant has previously been published in one patient with a clinical diagnosis of congenital LQTS (Tester et al., 2005). This variant has also been observed in one other unrelated individual with infantile onset LQTS referred for genetic testing at GeneDx, and was found to segregate with disease in one relative with a prolonged QT interval. The K526E variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). K526E is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Although in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function, functional studies by Tobelaim et al., (2017) suggest K526E may affect potassium channel gating and cause a reduction in current density. However, additional segregation data, functional evidence, and published cases are needed in order to definitively determine the role of this variant in disease.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
