ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.68527+1G>C

gnomAD frequency: 0.00001  dbSNP: rs766984722
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001217740 SCV001389592 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-08-17 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 946801). This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is present in population databases (rs766984722, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 322 of the TTN gene. It is expected to disrupt RNA splicing and likely results in a truncated or disrupted TTN protein.
GeneDx RCV003127692 SCV003803193 likely pathogenic not provided 2023-02-05 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Located in the A-band region of TTN in which the majority of loss of function variants have been associated with autosomal dominant titinopathies (Herman et al., 2012); This variant is associated with the following publications: (PMID: 22335739)

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