Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000157259 | SCV000752809 | uncertain significance | Long QT syndrome | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 252 of the KCNH2 protein (p.Arg252Gln). 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: 180380). 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 glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Clinical Genomics Laboratory, |
RCV003993839 | SCV004812251 | uncertain significance | Short QT syndrome type 1 | 2021-07-02 | criteria provided, single submitter | clinical testing | The p.Arg252Gln variant in the KCNH2gene has not been previously reported in association with disease.This variant has been identified in 2/64,380 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/).Notably, this region is indicated to have low coverage.The arginine at position 252 is poorly evolutionarily conserved and severalspecies have a glutamine at this position.Computational tools predict that the p.Arg252Gln variant is deleterious; however, the accuracy of in silicoalgorithms is limited.These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of thep.Arg252Glnvariant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PP3] |
| Blueprint Genetics | RCV000157259 | SCV000206989 | uncertain significance | Long QT syndrome | 2014-05-26 | no assertion criteria provided | clinical testing |