Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001906199 | SCV002170969 | pathogenic | Long QT syndrome | 2024-05-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu544Argfs*111) 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). This variant is not present in population databases (gnomAD no frequency). 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: 1397577). For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV003591901 | SCV004358338 | pathogenic | Cardiac arrhythmia | 2023-06-29 | criteria provided, single submitter | clinical testing | This variant causes a duplication of 1 nucleotide in exon 7 of the KCNH2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with KCNH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of KCNH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| All of Us Research Program, |
RCV001906199 | SCV004829952 | pathogenic | Long QT syndrome | 2024-09-18 | criteria provided, single submitter | clinical testing | The c.1629dup (p.Glu544Argfs*111) variant in KCNH2 gene, that encodes for potassium voltage-gated channel subfamily H member 2, creates a premature termination codon that is predicted to lead to absent or truncated protein product. To our knowledge, this variant has not been reported in individuals with KCNH2-related conditions in the literature. Loss-of-function variants in KCNH2 are well known to be pathogenic and ClinGen score shows sufficient evidence of haploinsufficiency of this gene (PMID:18774102, 24530480, 10973849, 19862833). This variant is absent in the general population database gnomAD v4.1.0. Loss-of-function variants downstream of this variant are reported to be pathogenic in individuals with long QT syndrome (PMID: 16244680, 26669661) and classified as pathogenic by several ClinVar submitters (ClinVar ID: 648088, 943351, 526968). Therefore, the c.1629dup (p.Glu544Argfs*111) variant in KCNH2 gene is classified as pathogenic. |