Submissions for variant NM_001267550.2(TTN):c.51654C>G (p.Tyr17218Ter)

dbSNP: rs1131691655

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000494626	SCV000582572	pathogenic	not provided	2015-09-16	criteria provided, single submitter	clinical testing	The Y15577X variant in the TTN gene has not been reported previously as a pathogenic variant or as a benign variant, to our knowledge. This pathogenic variant is predicted to cause loss of normal protein function either due to production of an abnormal, prematurely truncated protein, or by absence of protein product due to nonsense mediated mRNA decay. Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012). However, Y15577X is located in the A-band region of titin, where the majority of pathogenic truncating variants associated with DCM have been reported (Herman et al., 2012). Furthermore, Y15577X was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, Y15577X in the TTN gene is interpreted as a pathogenic variant.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845452	SCV000987539	pathogenic	Primary familial dilated cardiomyopathy		criteria provided, single submitter	clinical testing