ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2323A>G (p.Met775Val) (rs199473546)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181916 SCV000234219 uncertain significance not provided 2016-06-13 criteria provided, single submitter clinical testing The M1115V variant has previously been published in one individual with LQTS and was absent from at least 2,600 control alleles in this study (Kapplinger et al., 2009). In addition, this variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the M1115V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species, and Valine is the wild-type amino acid at this position in multiple species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, only one missense variant a in nearby residue (A1116V) has been reported in the Human Gene Mutation Database in association with LQTS (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058219 SCV000089739 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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