ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.3379C>T (p.Leu1127Phe)

dbSNP: rs1800856518
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001843220 SCV001350648 uncertain significance Cardiac arrhythmia 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 1127 of the KCNH2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on 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 has not been identified in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002560857 SCV003489873 uncertain significance Long QT syndrome 2022-03-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1127 of the KCNH2 protein (p.Leu1127Phe). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 923705). 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).
Ambry Genetics RCV004033337 SCV005033226 uncertain significance Cardiovascular phenotype 2023-11-13 criteria provided, single submitter clinical testing The p.L1127F variant (also known as c.3379C>T), located in coding exon 15 of the KCNH2 gene, results from a C to T substitution at nucleotide position 3379. The leucine at codon 1127 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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