Description
p.Val115Gly (GTG>GGG): c.344 T>G in exon 3 of the KCNH2 gene (NM_000238.2). While the V115G mutation in the KCNH2 gene has not been reported to our knowledge as benign polymorphism, a mutation affecting this same residue, V115M, has been reported in association with LQTS (Nagaoka I et al., 2008). Additionally, mutations in nearby residues (D111V, P114S, M124R, M124T) have been reported in association with LQTS, further supporting the functional importance of this residue and this region of the protein. V115G results in a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico algorithms are not consistent in their predictions but at least two concur that V115G is possibly damaging to the protein structure/function. Furthermore, V115G 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.In summary, V115G in the KCNH2 gene is interpreted as a likely 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 |
