Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481174 | SCV000569953 | likely pathogenic | not provided | 2016-04-11 | criteria provided, single submitter | clinical testing | The Q695X variant in the KCNH2 gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. Q695X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other downstream truncating variants in the KCNH2 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the Q695X likely pathogenic variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. |
| Labcorp Genetics |
RCV000631681 | SCV000752764 | pathogenic | Long QT syndrome | 2022-03-06 | 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: 420923). 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). This sequence change creates a premature translational stop signal (p.Gln695*) 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). |
| Ambry Genetics | RCV003168953 | SCV003864705 | pathogenic | Cardiovascular phenotype | 2023-01-18 | criteria provided, single submitter | clinical testing | The p.Q695* pathogenic mutation (also known as c.2083C>T), located in coding exon 8 of the KCNH2 gene, results from a C to T substitution at nucleotide position 2083. This changes the amino acid from a glutamine to a stop codon within coding exon 8. This variant has been detected in an individual from a long QT syndrome cohort (Walsh R et al. Genet Med, 2021 Jan;23:47-58). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |