ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.296A>G (p.Tyr99Cys) (rs199472854)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181947 SCV000234250 pathogenic not provided 2013-05-09 criteria provided, single submitter clinical testing p.Tyr99Cys (TAC>TGC): c.296 A>G in exon 2 of the KCNH2 gene (NM_000238.2)While the Tyr99Cys mutation in the KCNH2 gene has not been reported to our knowledge, a mutation affecting this same residue, Tyr99Ser, has been reported in association with LQTS (Jongbloed R et al., 2002). Additionally, mutations in nearby residues (Glu95Gly, Ile96Val, Arg100Gly) have been reported in association with LQTS, further supporting the functional importance of this codon and this region of the protein. Tyr99Cys results in a non-conservative amino acid substitution of a large Tyrosine residue with a small Cysteine residue. In silico analysis predicts Tyr99Cys is probably damaging to the protein structure/function. Furthermore, Tyr99Cys was not observed in approximately 6,300 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, Tyr99Cys in the KCNH2 gene is interpreted as a likely disease-causing mutation. The variant is found in LQT panel(s).

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