Description
p.Phe805Cys (TTT>TGT): c.2414 T>G in exon 10 of the KCNH2 gene (NM_000238.2)The Phe805Cys mutation in the KCNH2 gene has been reported previously in one individual diagnosed with LQTS (Splawski I et al., 2000). Functional studies have shown that Phe805Cys results in a trafficking defect and consequent reduced potassium channel current (Ficker E et al., 2002; Anderson C et al., 2006). Also, a mutation affecting this same residue, Phe805Ser, has been reported in association with LQTS and was absent from more than 400 control alleles in this study (Splawski I et al., 2000). Mutations in nearby residues (Gly800Glu, Gly800Trp, Gly806Glu) have been reported in association with LQTS, supporting the functional importance of this residue and this region of the protein. Furthermore, Phe805Cys was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, Phe805Cys in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
