Submissions for variant NM_001267550.2(TTN):c.30539-1G>A

dbSNP: rs768372747

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000492995	SCV000583305	uncertain significance	not provided	2017-05-22	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the TTN gene. The c.26807-1 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.26807-1 G>A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.26807-1 G>A splice site variant in the TTN gene destroys the canonical splice acceptor site for intron 106. It is predicted to cause abnormal gene splicing, either leading to 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 RNA/functional studies the actual effect of this change is unknown. Additionally, the c.26807-1 G>A variant is not located in the A-band nor the M-line region of titin, where the majority of pathogenic truncating variants have been reported. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.