Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000599154 | SCV000710054 | pathogenic | not provided | 2017-06-23 | criteria provided, single submitter | clinical testing | Although the c.2482_2491del10 pathogenic variant in the KCNH2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon cysteine 828, changing it to a threonine, and creating a premature stop codon at position 37 of the new reading frame, denoted p.Cys828ThrfsX37. 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 KCNH2 gene have been reported in Human Gene Mutation Database in association with LQTS (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.2482_2491del10 variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). |