ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.443G>A (p.Arg148Gln)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687344 SCV000814907 uncertain significance Long QT syndrome 2018-06-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 148 of the KCNH2 protein (p.Arg148Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs374912424, ExAC 0.02%). This variant has not been reported in the literature in individuals with KCNH2-related disease. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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