Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018347 | SCV004848033 | likely pathogenic | Congenital long QT syndrome | 2017-01-31 | criteria provided, single submitter | clinical testing | The p.Thr1019fs variant in KCNH2 has not been previously reported in individuals with long QT syndrome. Data from large population studies is insufficient to assess the frequency of this variant. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1019 and leads to a premature termination codon 102 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the KCNH2 gene is associated with long QT syndrome. In summary, although additional studies are required to fully establish its clinical significance, the p.Thr1019fs variant is likely pathogenic for long QT syndrome in an autosomal dominant manner based on its predicted impact to the protein. |