ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.80G>A (p.Arg27His) (rs199472828)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181921 SCV000234224 likely pathogenic not provided 2014-06-02 criteria provided, single submitter clinical testing p.Arg27His (CGT>CAT): c.80 G>A in exon 2 of the KCNH2 gene (NM_000238.2)While the R27H variant in the KCNH2 gene has not been reported to our knowledge, a mutation affecting this same residue, R27P, has been reported previously in one patient with LQTS, and was not reported in 200 Japanese control individuals (Itoh H et al., 2010). However, Itoh et al. did not report clinical information or segregation data for this patient and did not test for several other LQTS-related genes (Itoh et al., 2010). The R27H variant 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (S26I, K28E, F29S, F29L) have been reported in association with LQTS, supporting the functional importance of this residue and region of the protein. However, the R27H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in LQT panel(s).

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