Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000414451 | SCV000492372 | uncertain significance | not specified | 2016-12-12 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the KCNQ3 gene. The T856I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T856I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server. The T856I variant 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. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Labcorp Genetics |
RCV002521440 | SCV003469098 | uncertain significance | Benign neonatal seizures | 2022-08-04 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 373751). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 856 of the KCNQ3 protein (p.Thr856Ile). This variant is present in population databases (rs762078830, gnomAD 0.006%). |