ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.881G>T (p.Gly294Val) (rs199473549)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527846 SCV000627502 uncertain significance Long QT syndrome 2017-03-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 294 of the KCNH2 protein (p.Gly294Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. While this variant is not present in population databases (rs199473549), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an infant who died suddenly (PMID: 15913580). ClinVar contains an entry for this variant (Variation ID: 67539). This variant identified in the KCNH2 gene is located in the cytoplasmic N-terminal region of the resulting protein (PMID: 19841300, 25348405). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058268 SCV000089788 not provided SUDDEN INFANT DEATH SYNDROME no assertion provided literature only This variant has been reported as associated with Sudden infant death syndrome in the following publications (PMID:15913580). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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