ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1675C>T (p.Leu559Phe) (rs794728374)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181804 SCV000234107 pathogenic not provided 2014-02-05 criteria provided, single submitter clinical testing p.Leu559Phe (CTC>TTC): c.1675 C>T in exon 7 of the KCNH2 gene (NM_000238.2)While the L559F mutation in the KCNH2 gene has not been reported to our knowledge, a mutation affecting this same residue, L559H, has been reported in association with LQTS (Liu et al., 2002). Additionally, mutations in nearby residues (A558E, A558P, A561P, A561T, A561V) have been reported in association with LQTS, further supporting the functional importance of this residue and this region of the protein. L559F results in a conservative amino acid substitution as these residues share similar properties, and are least likely to impact secondary structure. The L559F residue is completely conserved across species and in silico analysis predicts L559F is damaging to the protein structure/function. Furthermore, L559F was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, L559F in the KCNH2 gene is interpreted as a likely disease-causing mutation. The variant is found in LQT panel(s).

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