ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.877G>T (p.Ala293Ser) (rs794728362)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181770 SCV000234073 uncertain significance not provided 2014-04-01 criteria provided, single submitter clinical testing p.Ala293Ser (CGC>TCC): c.877 G>T in exon 4 of the KCNH2 (HERG) gene (NM_000238.2). A variant of unknown significance has been identified in the KCNH2 gene. The A293S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A293S variant was not observed in approximately 1,800 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A293S variant is a non-conservative amino acid substitution which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Missense mutations in nearby residues (E289K, M291T, G294V, P297S) have been reported in association with LQTS, supporting the functional importance of this region of the protein. However, this substitution occurs at a residue that is not conserved across species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s).

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