Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187970 | SCV000241573 | uncertain significance | not provided | 2018-09-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the KCNQ3 gene. The V286I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V286I variant is observed in 8/30780 (0.03%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The V286I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000647889 | SCV000769693 | uncertain significance | Benign neonatal seizures | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 286 of the KCNQ3 protein (p.Val286Ile). This variant is present in population databases (rs549372035, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. ClinVar contains an entry for this variant (Variation ID: 205965). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNQ3 protein function. 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. |