ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1415G>C (p.Arg472Pro) (rs794728369)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181790 SCV000234093 likely pathogenic not provided 2012-06-08 criteria provided, single submitter clinical testing p.Arg472Pro (CGC>CCC): c.1415 G>C in exon 6 of the KCNH2 gene (NM_000238.2). The Arg472Pro variant in the KCNH2 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Arg472Pro results in a non-conservative amino acid substitution of a positively charged Arginine residue with a non-polar Proline residue at a position that is highly conserved throughout evolution. In silico analysis predicts Arg472Pro is probably damaging to the protein structure/function. Also, mutations in nearby codons (Asn470Asp, Thr473Asn,, Thr473Pro, Thr474Ile) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. The NHLBI ESP Exome Variant Server reports Arg472Pro was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.Therefore, while Arg472Pro is a good candidate for a disease-causing mutation. The variant is found in LQT panel(s).

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