ClinVar Miner

Submissions for variant NM_000238.3(KCNH2):c.3111C>T (p.Asp1037=) (rs200799870)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622008 SCV000737984 likely benign Cardiovascular phenotype 2017-04-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Athena Diagnostics Inc RCV000712077 SCV000842492 benign not provided 2018-03-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000712077 SCV000225760 uncertain significance not provided 2015-01-06 criteria provided, single submitter clinical testing
GeneDx RCV000225708 SCV000234044 benign not specified 2014-08-22 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.
Integrated Genetics/Laboratory Corporation of America RCV000225708 SCV000917557 benign not specified 2018-07-16 criteria provided, single submitter clinical testing Variant summary: KCNH2 c.3111C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00036 in 170308 control chromosomes, predominantly within the African subpopulation at a frequency of 0.004 in the gnomAD database, including 1 homozygote. The observed variant frequency within African control individuals in the gnomAD database is approximately 40 fold of the estimated maximal expected allele frequency for a pathogenic variant in KCNH2 causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.3111C>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (two classifying the variant as "Likely benign", and one as a VUS). Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000226655 SCV000283982 likely benign Long QT syndrome 2017-12-21 criteria provided, single submitter clinical testing

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