ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.442C>T (p.Arg148Trp) (rs139544114)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000148528 SCV000050827 benign Long QT syndrome 2013-06-24 criteria provided, single submitter research
GeneDx RCV000223902 SCV000234061 likely benign not specified 2017-01-23 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.
Invitae RCV000148528 SCV000253124 likely benign Long QT syndrome 2017-12-22 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000223902 SCV000539436 uncertain significance not specified 2016-04-25 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: Multiple reports as VUS/polymorphism, ExAC: 0.1% (99/66588) European chromosomes
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000223902 SCV000700686 likely benign not specified 2016-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618143 SCV000736190 benign Cardiovascular phenotype 2017-10-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with mutation in same gene (phase unknown),General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Color RCV000771377 SCV000903679 benign Arrhythmia 2018-03-16 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058234 SCV000089754 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19322600;PMID:19841300;PMID:21410720).
CSER_CC_NCGL; University of Washington Medical Center RCV000148528 SCV000190240 uncertain significance Long QT syndrome 2014-06-01 no assertion criteria provided research
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000223902 SCV000280131 uncertain significance not specified 2013-01-18 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. KCNH2 p.Arg148Trp Given the data reviewed below we also consider it a variant of uncertain significance. Millat et al (2009) observed the variant in a 4mo male SIDS case. Kapa et al (2009) report the variant as a polymorphism. They do not provide the frequency of the variant in controls but note that they considered something a polymorphism if it was seen more than once in the 1369 controls they studied. This same group reported the variant in a case of autopsy-negative sudden cardiac death but noted it was a "less common polymorphism" without functional data supporting pathogenicity. Novotny et al (2011) sequenced several long QT genes in individuals with coronary artery disease and ventricular fibrillation and observed this variant in one individual. Crotti et al (2012) reported the variant in one individual with long QT syndrome. No ancestry or segregation data were provided. The variant is in the N-terminal region of the protein. In total the variant has been seen in 25 of 7164 individuals in publicly available general population samples. The variant is listed in dbSNP (rs139544114), pointing to the NHLBI ESP data and also noting that ~9/661 individuals in the ClinSeq population from NIH (a general population cohort) were heterozygotes. The variant was reported online in 16 of 4300 Caucasian individuals and 0 of 2203 African-American individuals in the NHLBI Exome Sequencing Project dataset (as of January 18th, 2012). The phenotype of those individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension.

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