Submissions for variant NM_001267550.2(TTN):c.60399del (p.Ser20134fs)

dbSNP: rs727504466

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155591	SCV000205299	likely pathogenic	Primary dilated cardiomyopathy	2015-03-11	criteria provided, single submitter	clinical testing	The p.Ser17566fs variant in TTN has been identified by our laboratory in 1 Cauca sian adult with DCM and segregated with disease in 2 affected relatives. It was absent from large population studies. This variant is predicted to cause a frame shift, which alters the protein?s amino acid sequence beginning at position 1756 6 and leads to a premature termination codon 9 amino acids downstream. This alte ration is then predicted to lead to a truncated or absent protein. Frameshift an d other truncating variants in TTN are strongly associated with DCM, particularl y if they are located in the exons encoding for the A-band region of the protein (Herman 2012, Pugh 2014), where this variant is located. In summary, although a dditional studies are required to fully establish its clinical significance, the p.Ser17566fs variant is likely pathogenic.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768972	SCV000900345	likely pathogenic	Cardiomyopathy	2015-12-03	criteria provided, single submitter	clinical testing