ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.274C>T (p.Arg92Cys) (rs563611707)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181942 SCV000234245 uncertain significance not provided 2016-11-01 criteria provided, single submitter clinical testing p.Arg92Cys (CGC>TGC): c.274 C>T in exon 2 of the KCNH2 gene (NM_000238.2). The R92C variant in the KCNH2 gene has been observed in an individual with repaired Tetralogy of Fallot; however, this individual was not reported to have a history of cardiac life-threatening events and no specific clinical or functional studies were provided (Chiu et al., 2012). Additionally, the R92C variant was observed in approximately 0.2% (7/4120) alleles from individuals of East Asian background in the Exome Aggregation Consortium (ExAC) data set, further supporting that it may be a rare (benign) variant. Nevertheless, R92C is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. This substitution occurs at a position that is conserved across species. Consequently, in silico analysis predicts R92C is damaging to the protein structure/function. Although variants in nearby residues (E90K, E90Q, V94M) have been reported in HGMD in association with LQTS (Stenson et al., 2014), the pathogenicity of these variants have not been definitively determined. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.

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