ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1760G>T (p.Trp587Leu) (rs794728399)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181895 SCV000234198 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNH2 gene. The W927L variant has not been published as pathogenic or been reported as benign to our knowledge. Data from control individuals were not available to assess whether W927L may be a common benign variant in the general population. Nevertheless, the W927L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Finally, this substitution occurs at a position that is conserved in mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae RCV000540197 SCV000627469 uncertain significance Long QT syndrome 2017-09-29 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with leucine at codon 927 of the KCNH2 protein (p.Trp927Leu). The tryptophan residue is moderately conserved and there is a small physicochemical difference between tryptophan and leucine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KCNH2-related disease. ClinVar contains an entry for this variant (Variation ID: 200501). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000181895 SCV000924818 uncertain significance not provided 2016-03-11 no assertion criteria provided provider interpretation

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