ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.86799_86802del (p.Glu28935_Gly28936insTer) (rs727504856)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156206 SCV000205922 likely pathogenic Primary dilated cardiomyopathy 2014-07-21 criteria provided, single submitter clinical testing The Gly26368X variant in TTN has been identified by our laboratory in 1 young ad ult with DCM. It was absent from large population studies. This variant is predi cted to cause a frameshift which leads to a premature termination codon at posit ion 26368. This alteration is then predicted to lead to a truncated or absent pr otein. Frameshift and other truncating variants in TTN are strongly associated w ith DCM and the majority occur in the A-band (Herman 2012, Pugh 2014), where thi s variant is located. In summary, although additional studies are required to fu lly establish its clinical significance, the Gly26368X variant is likely pathoge nic.
Genetic Services Laboratory, University of Chicago RCV000501735 SCV000597685 pathogenic not provided 2016-07-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000501735 SCV000704296 likely pathogenic not provided 2016-12-20 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845492 SCV000987590 pathogenic Primary familial dilated cardiomyopathy criteria provided, single submitter clinical testing
Invitae RCV001204749 SCV001375969 likely pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-02-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TTN gene (p.Gly28936*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 179417). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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