Submissions for variant NM_001267550.2(TTN):c.12517G>T (p.Glu4173Ter)

dbSNP: rs1131691288

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000727393	SCV000581792	uncertain significance	not provided	2017-04-24	criteria provided, single submitter	clinical testing	The E3856X variant in the TTN gene has not been reported as a pathogenic or benign variant to our knowledge. Furthermore, it is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other nonsense variants in the TTN gene have been reported in Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014). Nevertheless, the majority of pathogenic variants reported in association with autosomal dominant dilated cardiomyopathy (DCM) are truncating variants in the A-band region of titin, while the clinical significance of variants in the I-band, where E3856X occurs, is not well characterized. Furthermore, truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012).
Eurofins Ntd Llc (ga)	RCV000727393	SCV000708139	uncertain significance	not provided	2017-05-30	criteria provided, single submitter	clinical testing