Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001939537 | SCV002233104 | pathogenic | Long QT syndrome | 2022-08-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1454593). This premature translational stop signal has been observed in individual(s) with long QT syndrome (PMID: 27920829). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1033Profs*23) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 10973849, 19862833). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001939537 | SCV005380646 | pathogenic | Long QT syndrome | 2024-08-12 | criteria provided, single submitter | clinical testing | Variant summary: KCNH2 c.3096_3099delGCGG (p.Arg1033ProfsX23) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 145380 control chromosomes. c.3096_3099delGCGG has been reported in the literature in at least one individual affected with Long QT Syndrome (e.g. Burns_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27920829). ClinVar contains an entry for this variant (Variation ID: 1454593). Based on the evidence outlined above, the variant was classified as pathogenic. |