ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.455C>G (p.Thr152Ser) (rs794728354)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181759 SCV000234062 uncertain significance not provided 2013-08-21 criteria provided, single submitter clinical testing p.Thr152Ser (ACC>AGC): c.455 C>G in exon 3 of the KCNH2 gene (NM_000238.2). The Thr152Ser variant in the KCNH2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Thr152Ser results in a conservative amino acid substitution of one neutral, polar amnio acid for another at a position that is not well conserved across species. In silico analysis predicts Thr152Ser is benign to the protein structure/function. However, mutations in nearby residues (Pro141Leu, Arg148Trp, Gly149Ala) have been reported in association with LQTS, supporting the functional importance of this region of the protein. The Thr152Ser 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.With the clinical and molecular information available at this time, we cannot definitively determine if Thr152Ser is a disease-causing mutation or a rare benign variant. The variant is found in LQT panel(s).
Color RCV000778034 SCV000914147 uncertain significance Arrhythmia 2018-10-11 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the cytoplasmic domain of the KCNH2 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 1/245546 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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