ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.383A>G (p.Asn128Ser) (rs200343670)

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Total submissions: 2
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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 RCV000171666 SCV000050695 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000556017 SCV000627490 uncertain significance Long QT syndrome 2017-04-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 128 of the KCNH2 protein (p.Asn128Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs200343670, ExAC 0.01%) but has not been reported in the literature in individuals with a KCNH2-related disease. ClinVar contains an entry for this variant (Variation ID: 191473). This variant identified in the KCNH2 gene is located in the cytoplasmic PAC region of the resulting protein (PMID: 19841300). For more information about the location of this variant, please visit www.invitae.com/KCNH2-topology. It is unclear how this variant impacts the function of this protein. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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