ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1282T>C (p.Ser428Pro) (rs794728368)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181787 SCV000234090 likely pathogenic not provided 2014-03-26 criteria provided, single submitter clinical testing p.Ser428Pro (TCG>CCG): c.1282 T>C in exon 6 of the KCNH2 (HERG) gene (NM_000238.2). While the S428P mutation in the KCNH2 gene has not been published to our knowledge, this mutation has been observed in one other unrelated individual tested for LQTS at GeneDx. Additionally, mutations affecting this same residue (S428L) and nearby residues (Y427H, Y427S, Y427C, A429P) have been reported in association with LQTS (Moss A et al, 2002; Napolitano C et al., 2005), supporting the functional importance of this residue and this region of the protein. In silico analysis predicts S428P is damaging to the protein structure/function. Furthermore, S428P was not observed in approximately 6500 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, S428P in the KCNH2 gene is interpreted as a likely disease-causing mutation. The variant is found in LQT, ARRHYTHMIA panel(s).

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