Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000604071 | SCV000713316 | likely pathogenic | Rare genetic deafness | 2017-06-09 | criteria provided, single submitter | clinical testing | The p.Val558ThrfsX3 (NM_004700.3 c.1671_1672insACGAC) variant in KCNQ4 has not b een previously reported in individuals with hearing loss and is absent from larg e population studies. This variant is predicted to cause a frameshift, which alt ers the protein?s amino acid sequence beginning at position 558 and leads to a p remature termination codon 3 amino acids downstream. This alteration is then pre dicted to lead to a truncated or absent protein. Heterozygous loss of function o f the KCNQ4 gene is an established disease mechanism in hearing loss. In summary , although additional studies are required to fully establish its clinical signi ficance, the p.Val558ThrfsX3 variant is likely pathogenic. |