ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.545C>T (p.Thr182Ile) (rs199472743)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001379437 SCV001577240 likely pathogenic Long QT syndrome 2020-07-29 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 309 of the KCNQ1 protein (p.Thr309Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Long QT syndrome (PMID: 11802537, 26118593, 9482580). ClinVar contains an entry for this variant (Variation ID: 53132). This variant identified in the KCNQ1 gene is located in the pore region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNQ1-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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057803 SCV000089323 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:11802537). 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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