ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.307G>A (p.Val103Ile)

dbSNP: rs1555874588
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 RCV000518985 SCV000619110 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNQ2 gene. The V103I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V103I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V103I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution alters a conserved position that is predicted to be within the transmembrane segment S1. 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.
Invitae RCV000697678 SCV000826303 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2021-01-14 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals with KCNQ2-related disease. ClinVar contains an entry for this variant (Variation ID: 450514). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 103 of the KCNQ2 protein (p.Val103Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine.

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.