Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760630 | SCV000890522 | likely pathogenic | not provided | 2018-07-13 | criteria provided, single submitter | clinical testing | The Q4339X likely pathogenic variant in the TTN gene has not been reported as a pathogenic or benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). The Q4339X variant is located in one of the constitutive exons in the proximal I-band region of the TTN gene and is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Recent studies have suggested that the truncating variants in the A-band (Herman et al., 2012) and in other constitutively expressed (percent spliced in PSI >95%) exons throughout the TTN gene are significantly associated with DCM (Deo et al., 2016; Schafer et al., 2017). |
Invitae | RCV002533841 | SCV003483362 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2021-12-18 | criteria provided, single submitter | clinical testing | 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). 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. ClinVar contains an entry for this variant (Variation ID: 620266). 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.Gln4656*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. |