ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.2567C>T (p.Thr856Ile)

gnomAD frequency: 0.00001  dbSNP: rs762078830
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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 (formerly Invitae), Labcorp 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%).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.