ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2119C>T (p.Arg707Cys) (rs377095107)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181913 SCV000234216 uncertain significance not provided 2018-03-16 criteria provided, single submitter clinical testing The R1047C variant in the KCNH2 gene has been reported previously in a single individual in a long QT syndrome cohort study (Crotti et al., 2012). The R1047C variant is not observed in large population cohorts (Lek et al., 2016). The R1047C 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in nearby residues (D1043G, L1054F, L1049P) have been reported in the Human Gene Mutation Database in association with Long QT syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R1047C as a variant of uncertain significance.
Invitae RCV000148531 SCV000815111 uncertain significance Long QT syndrome 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1047 of the KCNH2 protein (p.Arg1047Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. While this variant is present in population databases (rs377095107), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual affected with long QT syndrome (LQTS) (PMID: 23158531). ClinVar contains an entry for this variant (Variation ID: 161255). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
CSER _CC_NCGL, University of Washington RCV000148531 SCV000190243 uncertain significance Long QT syndrome 2014-06-01 no assertion criteria provided research

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.