Submissions for variant NM_001267550.2(TTN):c.76157_76158delinsAGGG (p.Gly25386fs)

dbSNP: rs794729341

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184331	SCV000236956	pathogenic	not provided	2014-02-14	criteria provided, single submitter	clinical testing	c.71234_71235delGAinsAGGG: p.Gly23745GlufsX31 (G23745EfsX31) in exon 276 of the TTN gene (NM_001256850.1). The normal sequence with the bases that are deleted in braces and inserted in brackets is: GCTG{GA}[AGGG]CTTA.Although the c.71234_71235delGAinsAGGG mutation in the TTN gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at codon Glycine 23745, changing it to an Glutamic acid, and creating a premature stop codon at position 31 of the new reading frame, denoted p.Gly23745GlufsX31. This mutation is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman D et al., 2012). However, c.71234_71235delGAinsAGGG is located in the A-band region of titin, where the majority of truncating mutations associated with DCM have been reported (Herman D et al., 2012). In summary, c.71234_71235delGAinsAGGG in the TTN gene is interpreted as a disease-causing mutation. The variant is found in DCM-CRDM panel(s).