Submissions for variant NM_172056.2(KCNH2):c.77-1G>A (rs794728406)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181919	SCV000234222	likely pathogenic	not provided	2016-08-19	criteria provided, single submitter	clinical testing	the c.77-1 G>A variant has not been reported as a pathogenic variant or as a benign variant to our knowledge. However, this variant has been identified in conjunction with an additional cardiogenetic variant in one individual referred for LQTS genetic testing at GeneDx. So far, segregation data is limited or absent for this individual due to the lack of clinical information provided and/or insufficient participation by informative family members. The c.77-1 G>A variant destroys the canonical splice acceptor site in intron 1 and is predicted to cause abnormal gene splicing. This variant is predicted to 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. Other splice site variants in the KCNH2 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the c.77-1 G>A 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.