ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter) (rs878854299)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231913 SCV000286600 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2016-01-16 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000657941 SCV000338622 uncertain significance not provided 2018-02-06 criteria provided, single submitter clinical testing
GeneDx RCV000657941 SCV000779710 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing The E11932X variant in the TTN gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The E11932X variant is not observed in large population cohorts (Lek et al., 2016). We interpret E11932X as a variant of uncertain significance.
Broad Institute Rare Disease Group, Broad Institute RCV000663407 SCV000786695 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy criteria provided, single submitter research The heterozygous p.Glu11932X variant in TTN has been identified in the compound heterozygous state by our project in one individual with early onset myopathy. The p.Glu11932X variant has not been reported in the literature however, it has been reported as a VUS for dilated cardiomyopathy in ClinVar. The lab reportedly identified this variant in 2 individuals, though no additional evidence was provided. Compound heterozygous loss of function TTN variants have been reported in individuals with early onset myopathy and cardiomyopathy. This variant has been identified in <0.01% (2/92728) of European chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs768073446). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. In summary, while the predicted impact of this variant provides some suspicion for a pathogenic role, the clinical significance of the p.Glu11932X variant is uncertain.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000657941 SCV001152960 likely pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing

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