ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.24385G>T (p.Glu8129Ter)

dbSNP: rs727504843
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156186 SCV000205902 likely pathogenic Primary dilated cardiomyopathy 2013-11-11 criteria provided, single submitter clinical testing The Glu6885X variant in TTN has not been previously reported in individuals with cardiomyopathy or in large population studies. This variant leads to a prematur e termination codon at position 6885, which is predicted to lead to a truncated or absent protein. Nonsense and other truncating variants in TTN are strongly as sociated with DCM and the majority occur in the A-band (Herman 2012, LMM unpubli shed data), while this variant occurs in the I-band. In summary, this variant is likely to be pathogenic, though additional studies are required to fully establ ish its clinical significance.
Invitae RCV001054543 SCV001218862 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2022-10-24 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 179397). This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu8129*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein.

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