ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.2369T>C (p.Leu790Pro)

dbSNP: rs1801084514
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001327902 SCV001518995 likely pathogenic Long QT syndrome 2022-11-21 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects KCNH2 function (Victor Chang Cardiac Research Institute). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1027323). This missense change has been observed in individuals with clinical features of Long QT syndrome (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 790 of the KCNH2 protein (p.Leu790Pro).
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations RCV002285475 SCV002575089 likely pathogenic Long QT syndrome 2 2021-10-28 criteria provided, single submitter clinical testing We observed de novo genetic variant NM_000238:c.2369T>C (p.Leu790Pro) in the KCNH2 gene in a male proband of 9 y.o. with QT interval prolongation on ECG (QTc 493 ms). This variant is not present in databases (gnomAD, LOVD). Multiple computational resources predict deleterious effect of p.Leu790Pro variant and intolerance of missense variants of the KCNH2 gene. Based on this evidence, we consider it to classify the p.Leu790Pro variant as Likely Pathogenic.

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