ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.551_559GCGCGGGCG[1] (p.184_186GAG[1]) (rs551056698)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181957 SCV000234260 likely benign not specified 2017-11-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239172 SCV000296888 likely benign Long QT syndrome 2 2015-10-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000247712 SCV000319803 benign Cardiovascular phenotype 2016-12-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance,Subpopulation frequency in support of benign classification,Structural Evidence,Other data supporting benign classification
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000181957 SCV000539434 uncertain significance not specified 2016-03-31 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Poor coverage; Reported in 4 probands; ExAC: 0.2% (12/6666) South Asian - does not pass filter
Invitae RCV000590741 SCV000555913 benign not provided 2019-02-23 criteria provided, single submitter clinical testing
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000584789 SCV000692516 likely benign Long QT syndrome 1 2017-03-16 criteria provided, single submitter research The KCNH2 Gly187_Gly189del is a 9 bp in-frame deletion. We identified this variant in a proband with Long QT syndrome, and no family history of disease or SCD. This variant was present at high frequency in the 1000 genomes project (MAF= 0.0028; http://www.1000genomes.org/), as well as the Exome Aggregation Consortium dataset (MAF= 0.008; http://exac.broadinstitute.org/). Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to be tolerated. In summary, based on high frequency in general populations and in silico tools predicting no affect on the protein, we classify the KCNH2 Gly187_Gly189del variant as "likely benign".
Integrated Genetics/Laboratory Corporation of America RCV000590741 SCV000696035 benign not provided 2017-02-06 criteria provided, single submitter clinical testing Variant summary: The KCNH2 c.560_568delGCGCGGGCG (p.Gly187_Gly189del) variant involves an in-frame deletion of 9 nucleotides. One in silico tool predicts a benign outcome for this variant, which was confirmed by an in vitro electrophysiology study (Mannikko_2010). This variant was found in 15/10674 control chromosomes at a frequency of 0.0014053, which is approximately 14 times the estimated maximal expected allele frequency of a pathogenic KCNH2 variant (0.0001), suggesting this variant is likely a benign polymorphism. This variant has been reported in multiple individuals without clinical information(Shimizu_2009, Goldenberg_2011, Itoh_2016). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. One internal sample carries this variant and KCNQ1 c.502G>A (pathogenic). Taken together, this variant is classified as benign.
Athena Diagnostics Inc RCV000590741 SCV000842499 benign not provided 2018-05-01 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768245 SCV000898772 uncertain significance Short QT syndrome 1; Long QT syndrome 2 2018-10-24 criteria provided, single submitter clinical testing KCNH2 NM_000238.3 exon 4 p.Gly187_Gly189del (c.560_568delGCGCGGGCG):This variant has been reported in the literature in at least 2 individuals with arrhythmia (i.e. sudden cardiac death, Long QT syndrome) (Shimizu 2009 PMID:19926013, Novotny 2011 PMID:21410720). This variant is present in 0.8% (76/9382) of African alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad-old.broadinstitute.org/variant/7-150655494-GCGCCCGCGC-G). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign (Variation ID:200600). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame deletion of 3 amino acids at position 187 within a repetitive region and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000590741 SCV001155314 likely benign not provided 2016-10-01 criteria provided, single submitter clinical testing

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.