ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.107202_107203del (p.Trp35735fs)

dbSNP: rs1575189496
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008504 SCV001168276 pathogenic not provided 2019-01-08 criteria provided, single submitter clinical testing The c.102279_102280delAT variant in the TTN gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.102279_102280delAT variant causes a frameshift starting with codon Tryptophan 34094, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Trp34094ValfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.102279_102280delAT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.102279_102280delAT as a pathogenic variant.
Invitae RCV001219294 SCV001391227 likely pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2019-05-27 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TTN gene (p.Trp35735Valfs*2). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. 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. 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). This variant has not been reported in the literature in individuals with TTN-related conditions.

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