ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.729C>A (p.Ser243Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002382718 SCV002671561 uncertain significance Cardiovascular phenotype 2022-03-08 criteria provided, single submitter clinical testing The p.S243R variant (also known as c.729C>A), located in coding exon 4 of the KCNH2 gene, results from a C to A substitution at nucleotide position 729. The serine at codon 243 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in an epilepsy cohort (Li X et al. Ann Hum Genet, 2020 03;84:161-168). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003103385 SCV003274667 uncertain significance Long QT syndrome 2023-08-30 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 243 of the KCNH2 protein (p.Ser243Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1758143). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. This variant is not present in population databases (gnomAD no frequency).

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