ClinVar

Description

The c.2692+5 G>T variant has not been reported as a pathogenic variant or as a benign variant to our knowledge. In silico splice site analysis algorithms predict that this variant destroys the natural splice donor site of intron 11, which may cause abnormal gene splicing. This variant may lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. The c.2692+5 G>T variant occurs at a nucleotide that is conserved across species. Multiple downstream truncating variants in the KCNH2 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the c.2692+5 G>T variant 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.Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.