ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.440A>G (p.His147Arg) (rs768938134)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181757 SCV000234060 uncertain significance not provided 2012-06-22 criteria provided, single submitter clinical testing p.His147Arg (CAC>CGC): c.440 A>G in exon 3 of the KCNH2 gene (NM_000238.2). The His147Arg variant in the KCNH2 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. His147Arg results in a conservative substitution of one positively charged amino acid for another at a residue that is not conserved across species. As a result, in silico analysis predicts His147Arg probably has a benign effect on the protein structure/function. While this information indicates His147Arg is likely benign, the NHLBI ESP Exome Variant Server reports His147Arg was not observed in approximately 5,00samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, the clinical significance of His147Arg in the KCNH2 gene is currently unknown. The variant is found in LQT panel(s).
Fulgent Genetics,Fulgent Genetics RCV000765949 SCV000897370 uncertain significance Short QT syndrome 1; Long QT syndrome 2 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000811589 SCV000951863 uncertain significance Long QT syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 147 of the KCNH2 protein (p.His147Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs768938134, ExAC 0.08%). This variant has not been reported in the literature in individuals with KCNH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 200285). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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