Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523415 | SCV000617201 | pathogenic | not provided | 2017-08-11 | criteria provided, single submitter | clinical testing | Although the c.657dupG pathogenic variant in the KCNQ1 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Glutamine 220, changing it to an Alanine, and creating a premature stop codon at position 65 of the new reading frame, denoted p.Gln220AlafsX65. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the KCNQ1 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the c.657dupG variant was not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server), indicating it is not a common benign variant.In summary, c.657dupG in the KCNQ1 gene is interpreted as pathogenic, as loss of function variants in this gene are strongly associated with this phenotype. |
| Labcorp Genetics |
RCV005091203 | SCV005843728 | pathogenic | Long QT syndrome | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln220Alafs*65) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 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 KCNQ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 449283). For these reasons, this variant has been classified as Pathogenic. |