ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.3400C>T (p.Arg1134Ter)

gnomAD frequency: 0.00001  dbSNP: rs965259777
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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 RCV001843185 SCV001349615 uncertain significance Cardiac arrhythmia 2023-05-10 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 15 of the KCNH2 gene, creating a premature translation stop signal in the last exon. The mutant protein is expected to escape nonsense-mediated decay and be expressed as a truncated protein product. To our knowledge, this variant has not been reported in individuals affected with KCNH2-related disorders in the literature. This variant has been identified in 2/201020 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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.
Invitae RCV001218764 SCV001390664 uncertain significance Long QT syndrome 2022-02-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1134*) in the KCNH2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the KCNH2 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 923242). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Ambry Genetics RCV003284023 SCV004009228 uncertain significance Cardiovascular phenotype 2023-04-13 criteria provided, single submitter clinical testing The p.R1134* variant (also known as c.3400C>T), located in coding exon 15 of the KCNH2 gene, results from a C to T substitution at nucleotide position 3400. This changes the amino acid from an arginine to a stop codon within coding exon 15. This alteration occurs at the 3' terminus of theKCNH2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 26 amino acids (2.2%) of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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