Submissions for variant NM_000238.4(KCNH2):c.551GCGCGGGCG[1] (p.184GAG[1])

dbSNP: rs551056698

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000590741	SCV000234260	benign	not provided	2022-04-08	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, 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	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory for Molecular Medicine, Mass General Brigham 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
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080836	SCV000555913	benign	Long QT syndrome	2025-01-30	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".
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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	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 type 1; Long QT syndrome 2	2021-03-30	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 Center for Human Genetics Tuebingen	RCV000590741	SCV001155314	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	KCNH2: BS1, BS2
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000181957	SCV001433427	benign	not specified	2019-11-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590741	SCV004563145	likely benign	not provided	2023-10-16	criteria provided, single submitter	clinical testing