ClinVar Miner

Submissions for variant NM_001256850.1(TTN):c.30895+1G>A (rs794727043)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000493981 SCV000225466 uncertain significance not provided 2016-04-11 criteria provided, single submitter clinical testing
Invitae RCV000473656 SCV000542722 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-04-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 122 of the TTN gene. It is expected to disrupt mRNA splicing and while this is not anticipated to result in nonsense mediated decay, it likely results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 193963). This variant identified in the TTN gene is located in the I band of the resulting protein (PMID: 25589632). Truncating variants in this region of the TTN gene 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 congenital myopathy (PMID: 23975875). 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.
GeneDx RCV000493981 SCV000583261 likely pathogenic not provided 2018-04-03 criteria provided, single submitter clinical testing The c.30895+1G>A variant in the TTN gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 119. This variant, located within the I-band region of the protein, is predicted to cause abnormal gene splicing resulting in an in-frame shortened protein product associated with an abnormal message. The c.30895+1G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.30895+1G>A as a likely pathogenic variant.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000493981 SCV000924997 uncertain significance not provided 2017-01-17 no assertion criteria provided provider interpretation

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