ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1444G>C (p.Val482Leu) (rs121912506)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181866 SCV000234169 likely pathogenic not provided 2017-06-15 criteria provided, single submitter clinical testing p.Val822Leu (GTG>CTG): c.2464 G>C in exon 10 of the KCNH2 (aka HERG) gene (NM_000238.2)While the Val822Leu variant in the KCNH2 gene has not been reported to our knowledge, a variant affecting this same codon, Val822Met, has been reported in association with LQTS. Additionally, variants in nearby residues (Ser818Pro, Gly820Arg, Arg823Trp, Thr826Ile) have been reported in association with LQTS, further supporting the functional importance of this codon and this region of the protein. Val822Leu results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved across species. In silico analysis predicts Val822Leu is probably damaging to the protein structure/function. Furthermore, Val822Leu was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. In summary, Val822Leu in the KCNH2 gene is interpreted as a likely pathogenic variant.

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